期刊
JOURNAL OF CANCER
卷 6, 期 9, 页码 843-848出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.12491
关键词
Salmonella; cancer therapy; tumor-targeting; breast cancer; BALB-neuT; autochthonous; spontaneous; 4T1; vasculature disruption; necrosis; combretastatin A-4
类别
资金
- ProjectStealth.org, StoneArch
- Randy Shaver Cancer Research and Community Fund
- Department of Surgery at the University of Minnesota
- ASL Cancer Research Fund
Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has been developed as a vector to deliver therapeutic agents to tumors. The potential of S. Typhimurium in cancer therapy is largely due to its reported propensity to accumulate at greater than 1,000-fold higher concentrations in tumors relative to healthy tissues. In this study, we compared bacterial colonization of tumors in a subcutaneous transplantation model with a more clinically relevant autochthonous tumor model. Following intravenous administration of attenuated S. Typhimurium strain SL3261, we observed approximately 10,000-fold less bacteria in autochthonous tumors that sporadically develop in transgenic BALB-neuT mice compared to tumors developed from subcutaneous transplantation of 4T1 murine breast cancer cells in BALB/c mice. Treatment of BALB-neuT mice with a vasculature-disrupting agent (VDA) prior to bacterial treatment caused necrosis of tumor tissue and significantly increased the bacterial targeting of autochthonous tumors by approximately 1,000-fold. These observations emphasize the importance of appropriate model selection in developing bacteria-based cancer therapies and demonstrate the potential of combining VDA pre-treatment with bacteria to facilitate targeting of clinically relevant tumors.
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