ABSTRACT
BACKGROUND: Although adjuvant chemotherapy is established for patients with non-small-cell lung cancer (NSCLC), the long-term survival remains to be improved. Postsurgical circulating tumor DNA (ctDNA) analysis of resectable NSCLC may identify patients at high risk of recurrence after adjuvant chemotherapy and facilitate personalized therapy. METHODS: This analysis included 38 patients who underwent curative-intent resection and received adjuvant chemotherapy for NSCLC. ctDNA analyses of tumor tissue, and pre- and post-operative plasma samples were performed with next-generation sequencing targeting 425 cancer-relevant genes. We define a ctDNA positive event as at least one shared mutation identified simultaneously in the plasma and tumor specimens. The primary endpoint was recurrence-free survival (RFS). RESULTS: At least one somatic mutation was identified in the tumor tissue of all 38 patients. Tumor tissue-specific mutated ctDNA was detected in the preoperative plasma samples of 19 (50%) patients. ctDNA in preoperative plasma was in good accordance with that in tissue. ctDNA was detectable in the first post-operative pre-chemotherapy samples of 8 of 35 (22.9%) patients and was associated with inferior RFS (HR, 3.69; P = 0.033). ctDNA was detected in the first post-chemotherapy samples of 8 of 36 (22.2%) patients and was also associated with inferior RFS (HR, 8.76; P < 0.001). CONCLUSIONS: Postoperative and post-chemotherapy ctDNA is a promising prognostic marker for resected NSCLC. ctDNA analyses may define a subgroup that remains at high risk of relapse despite standard adjuvant chemotherapy, and may help to inform intensified therapeutic strategies.
ABSTRACT
Staphylococcus aureus is an important zoonotic pathogen that causes a variety of life-threatening diseases. The increasing emergence of drug resistance further complicates the treatment of S. aureus infections. The critical role of alpha-hemolysin (Hla) in virulence renders this toxin an ideal target for the development of anti-infective agents for S. aureus. Here, We found that resveratrol, a natural compound widely found in fruits without antibacterial activity, could effectively inhibit Hla expression via down-regulating the transcription of hla, the gene that encodes Hla, and RNAIII, the effector molecule of the agr system. The addition of resveratrol to a co-culture system of S. aureus and A549â¯cells significantly alleviated bacteria-mediated cellular injury. Furthermore, treatment with resveratrol effectively protected mice from S. aureus pneumonia. Our results established resveratrol as an effective Hla inhibitor that reduces Hla expression without antimicrobial activity and can be further developed into novel therapeutics against S. aureus infections.
