Tumor-targeting Salmonella typhimurium A1-R suppressed an imatinib-resistant gastrointestinal stromal tumor with c-kit exon 11 and 17 mutations. Issue 6 (June 2018)

• Record Type: Journal Article
• Authors: Miyake, Kentaro; Kawaguchi, Kei; Miyake, Masuyo; Zhao, Ming; Kiyuna, Tasuku; Igarashi, Kentaro; Zhang, Zhiying; Murakami, Takashi; Li, Yunfeng; Nelson, Scott D.; Bouvet, Michael; Elliott, Irmina; Russell, Tara A.; Singh, Arun S.; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Singh, Shree Ram; Endo, Itaru; Eilber, Fritz C.; Hoffman, Robert M.
• Is Part Of: Heliyon. Volume 4:Issue 6(2018)
• Publication Date: 2018-06
• Subjects: Biochemistry -- Cancer research -- Genetics -- Microbiology; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2018.e00643
• Languages: English
• ISSNs: 2405-8440

Abstract

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 mm 3 : 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.