Cancer metastasis directly eradicated by targeted therapy with a modified Salmonella typhimurium.
Cancer metastasis directly eradicated by targeted therapy with a modified Salmonella typhimurium.
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DOI：
10.1002/jcb.22078
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发表时间：
2009-04-15
影响因子：
4
通讯作者：
Hoffman, Robert M.
中科院分区：
文献类型：
--
作者：
Hayashi, Katsuhiro;Zhao, Ming;Yamauchi, Kensuke;Yamamoto, Norio;Tsuchiya, Hiroyuki;Tomita, Katsuro;Hoffman, Robert M.
关键词：
癌症转移是癌症的危及生命的方面，并且通常对标准治疗具有抗性。我们在这里报告了一个针对癌症转移的治疗策略，使用一种改良的鼠伤寒沙门氏菌菌株。转基因的S.鼠伤寒是氨基酸精氨酸和亮氨酸的营养缺陷型。这些突变阻止了正常组织中的生长，但不降低肿瘤细胞中的细菌毒力。肿瘤靶向菌株S.将称为A1-R并表达绿色荧光蛋白（GFP）的鼠伤寒沙门氏菌分别施用于人胰腺癌和纤维肉瘤的腋淋巴和腘淋巴结转移，以及裸鼠中纤维肉瘤的肺转移。细菌通过淋巴通道递送以靶向淋巴结转移，并通过尾静脉全身递送以靶向肺转移。癌细胞在细胞质中表达红色荧光蛋白（RFP），在细胞核中表达与组蛋白H2 B连接的GFP，从而能够对靶向转移性肿瘤的细菌进行颜色编码的实时成像。治疗7-21天后，转移灶被根除，无需化疗或任何其他治疗。未观察到不良反应。这一新的策略表明了用工程菌靶向和治疗癌症转移而不需要毒性化疗的临床潜力。
Cancer metastasis is the life-threatening aspect of cancer and is usually resistant to standard treatment. We report here a targeted therapy strategy for cancer metastasis using a modified strain of Salmonella typhimurium. The genetically modified strain of S. typhimurium is auxotrophic for the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in tumor cells. The tumor-targeting strain of S. typhimurium, termed A1-R and expressing green fluorescent protein (GFP), was administered to both axillary lymph and popliteal lymph node metastasis of human pancreatic cancer and fibrosarcoma, respectively, as well as lung metastasis of the fibrosarcoma in nude mice. The bacteria were delivered via a lymphatic channel to target the lymph-node metastases and systemically via the tail vein to target the lung metastasis. The cancer cells expressed red fluorescent protein (RFP) in the cytoplasm and GFP in the nucleus linked to histone H2B, enabling color-coded real-time imaging of the bacteria targeting the metastatic tumors. After 7–21 days of treatment, the metastases were eradicated without the need of chemotherapy or any other treatment. No adverse effects were observed. This new strategy demonstrates the clinical potential of targeting and curing cancer metastasis with engineered bacteria without the need of toxic chemotherapy.
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影响因子：
5.1
作者：
Lemmon, MJ;vanZijl, P;Brown, JM
通讯作者：
Brown, JM
影响因子：
15.9
作者：
Sznol, M;Lin, SL;King, I
通讯作者：
King, I
影响因子：
11.2
作者：
Arrach, Nabil;Zhao, Ming;McClelland, Michael
通讯作者：
McClelland, Michael
影响因子：
11.2
作者：
Yamamoto, N;Jiang, P;Hoffman, RM
通讯作者：
Hoffman, RM
DOI：
10.1073/pnas.251543698
发表时间：
2001-12-18
影响因子：
11.1
作者：
Dang, LH;Bettegowda, C;Vogelstein, B
通讯作者：
Vogelstein, B