EAPSI: Establishing cellular biomarker levels and biological function in lung Cancer

翼啶是一类新兴的代谢生物标志物，有望作为肺癌等恶性肿瘤的非侵入性指标。近年来在蝶啶检测方面的进展已经阐明了蝶啶的生物学功能，并在癌细胞系中建立了细胞水平。本研究旨在结合强大的检测平台，建立多种人类细胞系中蝶啶的细胞水平，以提出新的蝶啶在肺癌中的作用机制，并生成相应的可用于临床筛查的蝶啶谱。这些蝶啶谱将使临床从业者能够推进蝶啶验证研究，并促进将蝶啶诊断快速转化为临床实践，而机制阐明将使新的抗癌技术成为可能。该研究将与北京大学生物分离领域的顶尖专家刘胡伟博士合作进行，北京大学将提供世界一流的细胞培养设施。本研究将利用一种新型毛细管电泳-激光诱导荧光（CE-LIF）蝶啶检测技术，监测已建立的人肺癌细胞系和作为对照的正常人胚胎肾细胞中15种临床重要的蝶啶。蝶啶的功能将通过使用成熟的方法激活/抑制代谢途径来确定。细胞蝶啶水平也将被表征，以预测尿基质中临床报告的水平升高。液相色谱-串联质谱（LC-MS/MS）的同时分析将允许鉴定新的临床有用的蝶啶衍生物。蝶啶谱包括15种临床重要的蝶啶和任何新发现的蝶啶衍生物将作为一种新的诊断工具用于肺癌和控制胚胎肾细胞系。该奖项由国家科学基金会与中国科技部共同资助。

Pteridines are an emerging class of metabolic biomarkers that show promise as noninvasive indicators of malignancies such as lung cancer. Recent advancements in pteridine detection have elucidated the biological function of pteridines and establish cellular levels in cancer cell lines. Using a combination of powerful detection platforms, this study aims to establish cellular pteridines levels in multiple human cell lines in order to propose novel pteridine mechanisms in lung cancer and to generate corresponding pteridine profiles that can be used for clinical screening purposes. These pteridine profiles will enable clinical practitioners to advance pteridine validation studies and facilitate the rapid translation of pteridine diagnostics into clinical practice while mechanism elucidation will enable new anti-cancer technologies. This research will be conducted in collaboration with Dr. Huwei Liu, a leading expert in bioseparations, at Peking University which affords unique access to world-class cell culture facilities.This study will utilize a novel capillary electrophoresis - laser-induced fluorescence (CE-LIF) pteridine detection technique to monitor 15 clinically important pteridines in an established human lung cancer cell line and normal human embryonic kidney cells which will be used as a control. Pteridine functionality will be determined through activation/inhibition of metabolic pathways using well-established methods. Cellular pteridine levels will also be characterized to predicate the elevated levels clinically reported in urine matrices. Simultaneous analysis by liquid chromatography - tandem mass spectrometry (LC-MS/MS) will permit identification of new clinically useful pteridine derivatives. Pteridine profiles including the 15 clinically important pteridines and any newly identified pteridine derivatives will be produced for lung cancer and control embryonic kidney cell lines as a new diagnostic tool. This NSF EAPSI award is funded in collaboration with the Chinese Ministry of Science and Technology.