RESUMEN
Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.
Asunto(s)
Adenocarcinoma/patología , Adhesinas Bacterianas/metabolismo , Antígenos de Carbohidratos Asociados a Tumores/metabolismo , Adhesión Bacteriana , Neoplasias del Colon/patología , Fusobacterium nucleatum/fisiología , Lectinas/metabolismo , Adenocarcinoma/microbiología , Animales , Línea Celular Tumoral , Neoplasias del Colon/microbiología , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Interacciones Huésped-Patógeno , Humanos , Ratones Endogámicos BALB C , Modelos Biológicos , Unión ProteicaRESUMEN
BACKGROUND: Other than the Advanced Trauma Life Support course, usually run for postgraduate trainees, there are few trauma courses available for medical students. It has been shown that trauma teaching for medical students is sadly lacking within the undergraduate curriculum. We stated that students following formal teaching, even just theory and some practice in basic skills significantly improved their management of trauma patients. METHODS: Hadassah-Hebrew University in Israel runs an annual 2-week trauma course for final-year medical students. The focus is on hands-on practice in resuscitation, diagnosis, procedures, and decision making. After engaging a combination of instructional and interactive teaching methods including practice on simulated injuries that students must assess and treat through the 2 weeks, the course culminates in a disaster drill where students work alongside the emergency services to rescue, assess, treat, and transfer patients. The course is evaluated with a written precourse and postcourse test, an Objective Structured Clinical Examination and detailed feedback from the drill. RESULTS: We analyzed student feedback at the end of each course during a 6-year period from 2007 to 2012. Correct answers for the posttest results were higher each year with good reliability as assessed by Chronbach's α and with significant variation from pretest scores assessed using paired-samples t tests. Best scores were achieved in knowledge acquisition and practical skills gained. Students were also asked whether the course contributed to self-preparedness in treating trauma patients, and this consistently achieved high scores. CONCLUSION: We believe that students benefit substantially from the course and gain lasting skills and confidence in trauma management, decision making, and organizational skills. The course provides students with the opportunity to learn and ingrain trauma principles along Advanced Trauma Life Support guidelines and prepares them for practice as safe doctors. We advocate the global implementation of a student trauma training course as a mandatory educational initiative and propose our course format as a model for similar courses.