Gupta-Burt S, Shamkhani H, Reed E, Tarone R E, Allegra C J, Pai L H, Poirier M C
Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Epidemiol Biomarkers Prev. 1993 May-Jun;2(3):229-34.
Nucleated blood cell DNA samples from ovarian (n = 27) and breast (n = 25) cancer patients receiving either cis-diamminedichloroplatinum II (cisplatin) and/or diamminecyclobutanecarboxylatoplatinum II were examined for the presence of platinum drug bound to DNA during several cycles of therapy. Platinum-DNA adducts were quantitated by cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) and atomic absorbance spectroscopy, techniques that measure either a fraction of the intrastrand cis-diammineplatinum-d(ApG) and -d(GpG) adducts (ELISA) or the total platinum bound to DNA (atomic absorbance spectroscopy), respectively. For either the complete study, or for samples obtained during the early cycles, individuals with progressive disease had severalfold lower overall cisplatin-DNA ELISA-measurable adduct levels than the individuals with more favorable clinical responses (complete response, partial response, or stable disease), who were grouped together and termed nonprogressive disease. In the case of the ovarian cancer patients, who experienced a 59% rate of complete and partial response, the correlation of high adduct values with disease response was statistically significant by the Wilcoxon rank-sum test (P = 0.028). In contrast, the breast cancer patients achieved only an 11.5% rate of complete and partial response, and the correlation of high adduct formation with disease response was not statistically significant. Levels of total DNA-bound platinum, measured by atomic absorbance spectroscopy, showed no correlation with disease response for either cancer by any analysis. The study supports previous observations demonstrating a consistent correlation between high cisplatin-DNA ELISA measurements and positive clinical outcome in ovarian cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
对接受顺二氯二氨铂（顺铂）和/或二氨环丁烷羧酸铂治疗的卵巢癌患者（n = 27）和乳腺癌患者（n = 25）的有核血细胞DNA样本，在几个治疗周期中检测与DNA结合的铂类药物的存在情况。通过顺铂-DNA酶联免疫吸附测定（ELISA）和原子吸收光谱法对铂-DNA加合物进行定量，这两种技术分别测量链内顺二氨铂-d（ApG）和-d（GpG）加合物的一部分（ELISA）或与DNA结合的总铂量（原子吸收光谱法）。对于整个研究或早期周期获得的样本，疾病进展的个体其总体顺铂-DNA ELISA可测量的加合物水平比临床反应较好（完全缓解、部分缓解或疾病稳定）的个体低几倍，后者被归为一组并称为疾病无进展。在卵巢癌患者中，完全缓解和部分缓解率为59%，通过Wilcoxon秩和检验，高加合物值与疾病反应的相关性具有统计学意义（P = 0.028）。相比之下，乳腺癌患者的完全缓解和部分缓解率仅为11.5%，高加合物形成与疾病反应的相关性无统计学意义。通过原子吸收光谱法测量的与DNA结合的总铂水平，经任何分析均显示与两种癌症的疾病反应均无相关性。该研究支持了先前的观察结果，即高顺铂-DNA ELISA测量值与卵巢癌患者的阳性临床结果之间存在一致的相关性。（摘要截短于250字）
