Borek E, Waalkes T P, Gehrke C W
Cancer Detect Prev. 1983;6(1-2):67-71.
It was known for some time that cancer patients excrete in their urine elevated levels of modified nucleosides. From earlier work, we were able to show that most of these modified nucleosides originate from transfer RNA (tRNA). The modifications are achieved at the macromolecular level by enzymes after primary synthesis. Such modifications are highly specific and, therefore, when the modified nucleosides accumulate from the tRNA breakdown, they cannot be reinserted randomly by the polymerases and must be excreted. We found that the modifying enzymes are aberrantly hyperactive in every malignant tissue. We also found that there is abnormally high turnover of tRNA in malignant tissues, which is probably the source of the elevated levels of excretion products. Since these products originate from a cardinal component of the molecular biology of every cell, the determination of markers in the urine may be a universal indicator of malignancy. We are focusing on the use of these markers in syndromes whose diagnoses are otherwise difficult. Since the marker levels return to normal very soon after chemotherapy, such determinations can be used to monitor the effectiveness of therapy. Therefore, the clinical oncologists can adapt their protocols to the specific need of a patient.
一段时间以来，人们已知癌症患者尿液中排出的修饰核苷水平升高。从早期的研究工作中，我们能够表明这些修饰核苷大多源自转运核糖核酸（tRNA）。这些修饰是在初级合成后由酶在大分子水平上完成的。此类修饰具有高度特异性，因此，当修饰核苷从tRNA降解中积累时，它们无法被聚合酶随机重新插入，而必须被排出。我们发现，在每个恶性组织中，修饰酶都异常活跃。我们还发现，恶性组织中tRNA的周转异常高，这可能是排泄产物水平升高的来源。由于这些产物源自每个细胞分子生物学的一个基本成分，尿液中标志物的测定可能是恶性肿瘤的一个通用指标。我们正专注于在诊断困难的综合征中使用这些标志物。由于化疗后标志物水平很快恢复正常，此类测定可用于监测治疗效果。因此，临床肿瘤学家可以根据患者的具体需求调整治疗方案。
