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Science ; 358(6369): 1443-1448, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29170280

RESUMO

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


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/microbiologia , Antibacterianos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/microbiologia , Fusobacterium/efeitos dos fármacos , Metronidazol/farmacologia , Microbiota/efeitos dos fármacos , Adenocarcinoma/secundário , Animais , Antibacterianos/farmacologia , Bacteroides/efeitos dos fármacos , Carcinogênese , Neoplasias Colorretais/patologia , Fusobacterium/genética , Fusobacterium/isolamento & purificação , Células HT29 , Humanos , Neoplasias Hepáticas/microbiologia , Neoplasias Hepáticas/secundário , Metronidazol/uso terapêutico , Camundongos , Prevotella/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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