Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Electrophoresis. 2023 Feb;44(3-4):442-449. doi: 10.1002/elps.202200214. Epub 2022 Dec 7.
Early detection has led to increased survival for multiple cancers; however, the 5-year survival rate of oral carcinoma (OC) has remained at 40% for the last several decades. Screening for OC is routinely done via visual examinations, followed by tissue biopsy and laboratory testing. Point-of-care testing would be a more convenient and widely available alternative for at-risk individuals. Increased lactate production is a hallmark of many head-and-neck tumors, due to the Warburg Effect, where tumor cells favor glycolysis in the place of oxidative phosphorylation. To detect excess lactate, we have modified the commensal bacterium Escherichia coli Nissle 1917 to express fluorescent reporter genes in response to extracellular lactate. Administering this commensal as a mouth wash and subsequently collecting saliva for the detection of the reporter may allow for noninvasive, early detection of cancerous lesions in at-risk individuals. Furthermore, we demonstrate a new on-chip electrokinetic technique to recover these probiotic probes from model saliva fluid to improve the detection of reporter gene activation.
早期检测已经提高了多种癌症的存活率;然而,在过去几十年中,口腔癌 (OC) 的 5 年存活率仍保持在 40%。OC 的筛查通常通过目视检查进行,然后进行组织活检和实验室检测。即时检测将是一种更方便和广泛可用的高危个体替代方法。由于沃伯格效应,许多头颈部肿瘤的标志是乳酸产量增加,其中肿瘤细胞倾向于糖酵解而不是氧化磷酸化。为了检测过量的乳酸,我们已经修饰了共生细菌大肠杆菌 Nissle 1917,使其在细胞外乳酸的刺激下表达荧光报告基因。将这种共生细菌作为漱口剂给药,然后收集唾液以检测报告基因,可能允许对高危个体的癌性病变进行非侵入性的早期检测。此外,我们展示了一种新的片上电动技术,从模型唾液中回收这些益生菌探针,以提高报告基因激活的检测。