Tumor-targeting Salmonella typhimurium A1-R suppressed an imatinib-resistant gastrointestinal stromal tumor with c-kit exon 11 and 17 mutations

Kentaro Miyake, Kei Kawaguchi, Masuyo Miyake, Ming Zhao, Tasuku Kiyuna, Kentaro Igarashi, Zhiying Zhang, Takashi Murakami, Yunfeng Li, Scott D. Nelson, Michael Bouvet, Irmina Elliott, Tara A. Russell, Arun S. Singh, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chishima, Shree Ram Singh, Itaru EndoFritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Gastrointestinal stromal tumor (GIST) is a refractory disease in need of novel efficacious therapy. The aim of our study was to evaluate the effectiveness of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) using on a patient derived orthotopic xenograft (PDOX) model of imatinib-resistant GIST. The GIST was obtained from a patient with regional recurrence, and implanted in the anterior gastric wall of nude mice. The GIST PDOX mice were randomized into 3 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration [p.o.], daily, for 3 weeks); G3, S. typhimurium A1-R group (intravenous [i.v.] injection, weekly, for 3 weeks). All mice from each group were sacrificed on day 22. Relative tumor volume was estimated by laparotomy on day 0 and day 22. Body weight of the mouse was evaluated 2 times per week. We found that S. typhimurium A1-R significantly reduced tumor growth in contrast to the untreated group (P = 0.001). In addition, we found that S. typhimurium A1-R was more effective compared to imatinib (P = 0.013). Furthermore, Imatinib was not significantly effective compared to the control group (P = 0.462). These results indicate that S. typhimurium A1-R may be new effective therapy for imatinib-resistant GIST and therefore a good candidate for clinical development of this disease.

Original languageEnglish
Article numbere00643
JournalHeliyon
Volume4
Issue number6
DOIs
Publication statusPublished - 2018 Jun
Externally publishedYes

Keywords

  • Biochemistry
  • Cancer research
  • Genetics
  • Microbiology

ASJC Scopus subject areas

  • General

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  • Cite this

    Miyake, K., Kawaguchi, K., Miyake, M., Zhao, M., Kiyuna, T., Igarashi, K., Zhang, Z., Murakami, T., Li, Y., Nelson, S. D., Bouvet, M., Elliott, I., Russell, T. A., Singh, A. S., Hiroshima, Y., Momiyama, M., Matsuyama, R., Chishima, T., Singh, S. R., ... Hoffman, R. M. (2018). Tumor-targeting Salmonella typhimurium A1-R suppressed an imatinib-resistant gastrointestinal stromal tumor with c-kit exon 11 and 17 mutations. Heliyon, 4(6), [e00643]. https://doi.org/10.1016/j.heliyon.2018.e00643