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结直肠癌的持续性及抗生素反应分析

Analysis of persistence and antibiotic response in colorectal cancer.

作者信息

Bullman Susan, Pedamallu Chandra S, Sicinska Ewa, Clancy Thomas E, Zhang Xiaoyang, Cai Diana, Neuberg Donna, Huang Katherine, Guevara Fatima, Nelson Timothy, Chipashvili Otari, Hagan Timothy, Walker Mark, Ramachandran Aruna, Diosdado Begoña, Serna Garazi, Mulet Nuria, Landolfi Stefania, Ramon Y Cajal Santiago, Fasani Roberta, Aguirre Andrew J, Ng Kimmie, Élez Elena, Ogino Shuji, Tabernero Josep, Fuchs Charles S, Hahn William C, Nuciforo Paolo, Meyerson Matthew

机构信息

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

出版信息

Science. 2017 Dec 15;358(6369):1443-1448. doi: 10.1126/science.aal5240. Epub 2017 Nov 23.

Abstract

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with and its associated microbiome-including , , and species-is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with -associated colorectal cancer.

摘要

结直肠癌由恶性细胞、未转化细胞和微生物组成的复杂混合物构成。[具体细菌名称]是结直肠癌组织中最常见的细菌种类之一。在此我们表明,人类结直肠癌被[具体细菌名称]及其相关微生物群(包括[其他细菌名称]、[其他细菌名称]和[其他细菌名称]种类)定植在远端转移灶中得以维持,这表明配对的原发性和转移性肿瘤之间微生物群的稳定性。原位杂交分析显示,[具体细菌名称]在转移病灶中主要与癌细胞相关。人类原发性结肠腺癌的小鼠异种移植瘤在连续传代过程中被发现保留了存活的[具体细菌名称]及其相关微生物群。用抗生素甲硝唑治疗携带结肠癌异种移植瘤的小鼠可降低[具体细菌名称]负荷、癌细胞增殖和总体肿瘤生长。这些观察结果支持进一步研究抗菌干预作为[具体细菌名称]相关结直肠癌患者潜在治疗方法的可能性。

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Analysis of persistence and antibiotic response in colorectal cancer.结直肠癌的持续性及抗生素反应分析
Science. 2017 Dec 15;358(6369):1443-1448. doi: 10.1126/science.aal5240. Epub 2017 Nov 23.

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