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首页> 外文期刊>Urologic oncology >Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium Zhao M, Yang M, Li XM, Jiang P, Baranov E, Li S, Xu M, Penman S, Hoffman RM, AntiCancer, San Diego, CA.
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Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium Zhao M, Yang M, Li XM, Jiang P, Baranov E, Li S, Xu M, Penman S, Hoffman RM, AntiCancer, San Diego, CA.

机译：用表达GFP的鼠伤寒沙门氏菌的氨基酸营养缺陷型进行靶向肿瘤的细菌治疗赵M，杨M，李XM，姜P，巴拉诺夫E，李S，徐M，彭曼S，霍夫曼RM，抗癌，圣地亚哥，加利福尼亚。

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Here we report a genetically modified bacteria strain, Salmonella typhimurium A1, selected for anticancer activity in vivo. The strain grows in tumor xenografts. In sharp contrast, normal tissue is cleared of these bacteria even in immunodeficient athymic mice. S. typhimurium A1 is auxotrophic (Leu/Arg-dependent) but apparently receives sufficient support from the neoplastic tissue to grow locally. Whether additional genetic lesions are present is not known. In in vitro infection, the GFP-expressing bacteria grew in the cytoplasm of PC-3 human prostate cancer cells and caused nuclear destruction. These effects were visualized in cells labeled with GFP in the nucleus and red fluorescent protein in the cytoplasm. In vivo, the bacteria caused tumor inhibition and regression of xenografts visualized by whole-body imaging. The bacteria, introduced i.v. or intratumorally, invaded and replicated intracellularly in PC-3 prostate cancer cells labeled with red fluorescent protein grafted into nude mice. By day 15, S. typhimurium A1 was undetectable in the liver, lung, spleen, and kidney, but it continued to proliferate in the PC-3 tumor, which stopped growing. When the bacteria were injected intratumorally, the tumor completely regressed by day 20. There were no obvious adverse effects on the host when the bacteria were injected by either route. The S. typhimurium A1 strain grew throughout the tumor, including viable malignant tissue. This result is in marked contrast to bacteria previously tried for cancer therapy that were confined to necrotic areas of the tumor, which may account, in part, for the strain's unique antitumor efficacy.
机译：在这里，我们报告了一种转基因的细菌菌株鼠伤寒沙门氏菌A1，被选为体内抗癌活性。该菌株在肿瘤异种移植物中生长。与之形成鲜明对比的是，即使在免疫缺陷的无胸腺小鼠中，正常组织也清除了这些细菌。鼠伤寒沙门氏菌A1是营养缺陷型的（依赖Leu / Arg），但显然从肿瘤组织获得了足够的支持，可以局部生长。尚不清楚是否存在其他遗传损伤。在体外感染中，表达GFP的细菌在PC-3人前列腺癌细胞的细胞质中生长并引起核破坏。这些效应在细胞核中标记为GFP且细胞质中标记为红色荧光蛋白的细胞中可见。在体内，该细菌引起肿瘤抑制和通过全身成像显示的异种移植物消退。这种细菌通过静脉注射或在肿瘤内侵入并复制到移植有裸鼠的红色荧光蛋白标记的PC-3前列腺癌细胞内。到第15天，鼠伤寒沙门氏菌A1在肝，肺，脾和肾中未检出，但在PC-3肿瘤中继续增殖，并停止生长。当肿瘤内注射细菌时，肿瘤在第20天完全消退，当通过任一途径注射细菌时，对宿主没有明显的不利影响。鼠伤寒沙门氏菌A1菌株在整个肿瘤中生长，包括存活的恶性组织。该结果与先前尝试用于癌症治疗的细菌形成鲜明对比，这些细菌仅限于肿瘤的坏死区域，这可能部分解释了该菌株独特的抗肿瘤功效。

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