Tumor-targeting Salmonella typhimurium A1-R overcomes partial carboplatinum-resistance of a cancer of unknown primary (CUP)

Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Ming Zhao, Sintawat Wangsiricharoen, Kei Kawaguchi, Zhiying Zhang, Takashi Higuchi, Sahar Razmjooei, Yunfeng Li, Scott D. Nelson, Tara Russell, Arun Singh, Takashi Murakami, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chishima, Shree Ram Singh, Sant P. ChawlaFritz C. Eilber, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Cancer of unknown primary (CUP) is metastatic disease without a known primary and therefore very difficult to identify effective therapy. Previously, we demonstrated partial efficacy of Salmonella typhimurium A1-R (S. typhimurium A1-R) alone and carboplatinum alone (CAR) on a CUP patient tumor in the patient-derived xenograft (PDOX) model. The aim of the present study was to investigate the efficacy of S. typhimurium A1-R combined with CAR on the CUP PDOX model. The CUP tumors were implanted orthotopically into the left supraclavicular fossa of nude mice to match the site from which they were resected from the patient. CUP PDOX models were divided randomly into the following 4 groups after the tumor volume reached 100 mm3: G1: untreated group; G2: CAR (30 mg/kg, i.p., weekly, 2 weeks); G3: S. typhimurium A1-R (5x107 CFU/body, i.v., weekly, 2 weeks).; G4: S. typhimurium A1-R combined with CAR (S. typhimurium A1-R; 5x107 CFU/body, i.v., weekly, 2 weeks; CAR, 30 mg/kg, i.p., weekly, 2 weeks). Each group comprised 7 mice. All mice were sacrificed on day 15. Tumor volume and body weight were measured twice a week. S. typhimurium A1-R and CAR moderately inhibited tumor growth compared to the untreated group on day 15 (P < 0.001 and P < 0.001, respectively). S. typhimurium A1-R combined with CAR inhibited the tumor growth significantly more compared to S. typhimurium A1-R monotherapy or CAR monotherapy on day 15 (P = 0.004 and P = 0.001, respectively). The present report demonstrates that S. typhimurium A1-R can increase the efficacy of a standard drug used for CUP in a PDOX model.

Original languageEnglish
Pages (from-to)144-149
Number of pages6
JournalTissue and Cell
Volume54
DOIs
Publication statusPublished - 2018 Oct
Externally publishedYes

Keywords

  • Cancer of unknown primary
  • Carboplatinum efficacy
  • CUP
  • Nude mice
  • Patient-derived orthotopic xenograft
  • PDOX
  • Salmonella typhimurium A1-R

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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