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

蝶呤类化合物是一类新兴的代谢生物标志物，有望成为肺癌等恶性肿瘤的非侵入性指标。在蝶啶检测方面的最新进展已经阐明了蝶呤的生物学功能，并建立了癌细胞株的细胞水平。利用多种强大的检测平台，本研究旨在建立多种人类细胞系中的蝶啶类药物水平，以提出新的蝶啶类药物在肺癌中的作用机制，并生成可用于临床筛查的相应的蝶啶类药物谱。这些蝶呤图谱将使临床医生能够推进蝶呤验证研究，并促进将蝶呤诊断快速转化为临床实践，同时机制阐明将使新的抗癌技术成为可能。这项研究将与北京大学领先的生物分离专家刘虎伟博士合作进行，北京大学拥有世界一流的细胞培养设施。这项研究将利用一种新的毛细管电泳光诱导荧光(CE-LIF)蝶啶检测技术来监测已建立的人类肺癌细胞系和正常人类胚胎肾细胞中15种临床重要的蝶呤类化合物作为对照。蝶啶的功能性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用来预测临床上报道的尿基质中的升高水平。用LC-MS/MS同时分析将有助于鉴定新的临床上有用的蝶啶类化合物。包括15种临床重要的蝶啶类化合物和任何新发现的蝶啶类化合物在内的蝶啶类化合物将用于肺癌和控制胚胎肾细胞系作为一种新的诊断工具。该NSF EAPSI奖是与中国科技部合作资助的。

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.