MASS SPECTROMETRY OF URINARY NUCLEOSIDES

文献资料证实了核苷水平的潜在用途 癌症患者尿液作为诊断的“生物标志物” 以及癌症的监测。然而，目前的分析方法很容易 对干扰和缺乏必要的敏感度来量化“罕见” 核苷。因此，GCMS方法将用于量化选定的 稳定同位素稀释法测定癌症患者尿液中的核苷 以及亚稳态离子监测技术。此外，质谱学 将被用来确定癌症中未知核苷的结构 患者的尿液可能提供更好的生物化学了解 癌细胞的数量。 癌症患者的尿液将由我的临床合作者和 将包括乳腺癌、结肠癌患者的样本 和白血病。尿样将在确诊后采集，期间 治疗和后续治疗。然后将结果与 确定尿核苷作为尿毒症生物标志物的效用 癌症。 样品将使用本课程开发的方法进行制备和分析。 实验室。这些方法已经用正常人的尿液进行了测试。 现已准备好应用于临床研究。 本提案中描述的研究有可能提供1) 简便、无创、快速的癌症诊断方法2) 临床医生采用无创、安全的方法对患者进行随访 对治疗的反应，以及3)患者复发的迹象。

Literature references attest to the potential utility of nucleoside levels in the urine of cancer patients as "biological markers" for the diagnosis and monitoring of cancer. However, current methods of analysis are prone to interferences and lack the sensitivity necessary to quantate "rare" nucleosides. GCMS methods will, therefore, be used to quantate selected nucleosides in the urine of cancer patients by the stable isotope dilution and metastable ion monitoring techniques. In addition, mass spectrometry will be used to determine the structures of unknown nucleosides in cancer patient urine which may provide a better understanding of the biochemistry of cancer cells. Urine of cancer patients will be provided by my clinical collaborators and will include samples from persons with breast cancer, cancer of the colon and leukemia. Urine samples will be obtained upon diagnosis, during treatment and following therapy. Results will then be compared to determine the utility of urinary nucleosides as "biological markers" of cancer. Samples will be prepared and analyzed using methods developed in this laboratory. The methods have been tested using urine from normal persons and are now ready to be applied to clinical studies. The research described in this proposal has the potential of providing 1) a simple, noninvasive, rapid method for the diagnosis of cancer, 2) clinicians with a noninvasive and safe method for following the patients response to therapy, and 3) an indication of relapse by the patient.