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[肿瘤靶向性沙门氏菌VNP20009的抗肿瘤作用及其对肿瘤免疫微环境的影响]

[Anti-tumor effect and impact on tumor immune microenvironment of tumor-targeted Salmonella VNP20009].

作者信息

Han Yu-heng, Lai Xing-huan, Le Zi-wei, Hua Zi-chun

出版信息

Yao Xue Xue Bao. 2016 Sep;51(9):1417-22.

PMID:29924525
Abstract

Salmonella is a gram-negative bacterium that has an ability of tumor-targeting growth and proliferation. Attenuated Salmonella VNP20009 is a virulence genes-knockout bacterial strain based on Salmonella typhimurium, and it has an advantage of good therapeutic effect and low toxicity. One of the mechanisms of anti-tumor effect of VNP20009 is the induction of inflammatory reaction within tumor tissues. We used B16F10 melanoma model to investigate the mechanism of the anti-tumor effect of VNP20009. VNP20009 treatment effectively inhibited tumor growth and promoted the apoptosis and necrosis of tumor cells. VNP20009 increased the accumulation or infiltration of CD8(+) T cells and CD11b(+) monocytes within tumor tissue by raising the level of immune response and thus, induce the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) to kill tumor cells by breaking the immuno-evasion barrier in the tumor microenvironment.

摘要

沙门氏菌是一种革兰氏阴性细菌,具有肿瘤靶向生长和增殖的能力。减毒沙门氏菌VNP20009是一种基于鼠伤寒沙门氏菌的毒力基因敲除菌,具有治疗效果好、毒性低的优点。VNP20009抗肿瘤作用的机制之一是诱导肿瘤组织内的炎症反应。我们使用B16F10黑色素瘤模型来研究VNP20009抗肿瘤作用的机制。VNP20009治疗有效抑制肿瘤生长,促进肿瘤细胞凋亡和坏死。VNP20009通过提高免疫反应水平增加肿瘤组织内CD8(+) T细胞和CD11b(+)单核细胞的聚集或浸润,从而诱导肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)的产生,通过打破肿瘤微环境中的免疫逃逸屏障来杀死肿瘤细胞。

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1
[Anti-tumor effect and impact on tumor immune microenvironment of tumor-targeted Salmonella VNP20009].[肿瘤靶向性沙门氏菌VNP20009的抗肿瘤作用及其对肿瘤免疫微环境的影响]
Yao Xue Xue Bao. 2016 Sep;51(9):1417-22.
2
The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009.基因slyA、STM3120和htrA是VNP20009抗癌能力所必需的。
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Attenuated Salmonella VNP20009 mutant (ΔhtrA) is a promising candidate for bacteria-mediated tumour therapy in hosts with TNFR1 deficiency.减毒沙门氏菌VNP20009突变体(ΔhtrA)是TNFR1缺陷宿主中细菌介导肿瘤治疗的一个有前景的候选者。
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Topical treatment of all-trans retinoic acid inhibits murine melanoma partly by promoting CD8 T-cell immunity.全反式维甲酸的局部治疗通过促进CD8 T细胞免疫部分抑制小鼠黑色素瘤。
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Salmonella-mediated tumor-targeting TRAIL gene therapy significantly suppresses melanoma growth in mouse model.沙门氏菌介导的肿瘤靶向 TRAIL 基因治疗显著抑制小鼠模型中黑色素瘤的生长。
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Antitumor effect of VNP20009, an attenuated Salmonella, in murine tumor models.减毒沙门氏菌VNP20009在小鼠肿瘤模型中的抗肿瘤作用。
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Attenuated Salmonella engineered with an apoptosis-inducing factor (AIF) eukaryotic expressing system enhances its anti-tumor effect in melanoma in vitro and in vivo.用凋亡诱导因子(AIF)真核表达系统构建的减毒沙门氏菌增强了其在体外和体内对黑色素瘤的抗肿瘤作用。
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Chloroquine enhanced the anticancer capacity of VNP20009 by inhibiting autophagy.氯喹通过抑制自噬增强了 VNP20009 的抗癌能力。
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