MASS SPECTROMETRY OF URINARY NUCLEOSIDES

参考文献证实了核苷水平的潜在效用 在癌症患者的尿液中作为诊断的“生物标志物” 和癌症监测。 然而，目前的分析方法往往 干扰和缺乏必要的灵敏度量化“罕见” 核苷 因此，GCMS方法将用于定量选择的 用稳定同位素稀释法测定癌症患者尿中的核苷类化合物 和亚稳离子监测技术。 此外，质谱 将用于确定癌症中未知核苷的结构 患者尿液，可以更好地了解生物化学 癌细胞。 癌症患者的尿液将由我的临床合作者提供， 将包括乳腺癌、结肠癌、 和白血病 尿液样本将在诊断时获得， 治疗和后续治疗。 然后将结果与 确定尿核苷作为“生物标志物”的效用， 癌 将使用本研究中开发的方法制备和分析样品。 实验室 该方法已被测试使用尿液从正常人 并准备应用于临床研究。 本提案中所述的研究有可能提供：1） 简单、无创、快速的癌症诊断方法，2） 临床医生用一种非侵入性和安全的方法来跟踪病人 对治疗的反应，和3）患者复发的指示。

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.