Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model.

Takashi Murakami,Robert M Hoffman,Itaru Endo,Michael Bouvet,Yong Zhang,Takashi Chishima,Ming Zhao,Kuniya Tanaka,Yukihiko Hiroshima

doi:10.18632/oncotarget.6170

Abstract

Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.

Highlights

Colon cancer liver metastasis is often the lethal aspect of this disease [1]
Residual tumor fluorescence was detected on the surgical resection bed after bright-light surgery (BLS) of HT-29-red fluorescent protein (RFP) liver metastasis (Figure 1)
Isolated liver metastasis provides an opportunity for resection, but BLS very often results in residual cancer cells

Summary

INTRODUCTION

Colon cancer liver metastasis is often the lethal aspect of this disease [1]. Well-isolated metastases are candidates for surgical resection, but recurrence is common [2]. The bacteria, known as Streptococcus pyogenes [3,4,5], was found in cancer patients who had remission and was used for therapy in the late 19th and early 20th centuries [35], especially under William B. S. typhimurium A1-R was able www.impactjournals.com/oncotarget to inhibit or eradicate primary and metastatic tumors as monotherapy in nude mouse models of prostate [23, 24], breast [25,26,27], lung [28, 29], pancreatic [30,31,32,33,34], ovarian [35, 36] stomach [37], and cervical cancer [38], as well as sarcoma [39,40,41] and glioma [42,43], all of which are highly aggressive tumor models. The present report demonstrates adjuvant treatment efficacy of S. typhimurium A1-R after bright-light surgery (BLS) of liver metastasis

RESULTS AND DISCUSSION

MATERIALS AND METHODS

CONFLICTS OF INTEREST