Riccardi A, Danova M, Dionigi P, Gaetani P, Cebrelli T, Butti G, Mazzini G, Wilson G
Dipartimento di Medicina Interna e Terapia Medica, Policlinico San Matteo, Italy.
Br J Cancer. 1989 Jun;59(6):898-903. doi: 10.1038/bjc.1989.190.
During a 15-month period, we used in vivo bromodeoxyuridine (BUDR) infusion to study cell kinetics in 112 consecutive patients with various types of malignant tumours: acute leukaemia (50 patients), gastric cancer (42) and brain gliomas (20). The in vivo BUDR method requires that a single tumour sample be taken 4-6 h after infusion and that bivariate flow cytometry (FCM) be employed to measure simultaneously the percentage of BUDR-labelled cells (which are identified with a green fluorescent anti-BUDR monoclonal antibody) and their mean DNA content (following propidium iodide staining). This technique rapidly furnishes the labelling index (LI) and the DNA synthesis time (TS), from which the tumour potential doubling time (Tpot) and production rate (fractional turnover rate, FTR) are calculated. The procedure took 6-9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and 80 (72%) of the 112 patients, respectively. Correlations were sought between kinetic parameters and a number of pathological and clinical ones. In 34 patients with acute non-lymphoblastic leukaemias who were uniformly treated for remission (CR) induction and maintenance, proliferative activity, as measured by Tpot and FTR, was greater in responsive than in non-responsive patients, and in those who experienced CR for over 8 months than in those who had a shorter CR. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease. No correlations between kinetic and clinical and pathological parameters were found in gliomas. These data indicate the in vivo BUDR infusion coupled with FCM measurements can be performed in clinical settings to obtain kinetic data rapidly in quite large patient series. This will probably allow the inclusion of kinetic data in clinical trials aimed at evaluating the prognostic relevance of these data.
在15个月的时间里，我们采用体内注射溴脱氧尿苷（BUDR）的方法，对112例连续的患有各种恶性肿瘤的患者进行细胞动力学研究，这些患者包括急性白血病（50例）、胃癌（42例）和脑胶质瘤（20例）。体内BUDR方法要求在注射后4 - 6小时采集单个肿瘤样本，并采用双变量流式细胞术（FCM）同时测量BUDR标记细胞的百分比（用绿色荧光抗BUDR单克隆抗体识别）及其平均DNA含量（碘化丙啶染色后）。该技术可快速提供标记指数（LI）和DNA合成时间（TS），并据此计算肿瘤潜在倍增时间（Tpot）和产生率（分数周转率，FTR）。该过程耗时6 - 9小时完成，且注射BUDR后无即刻毒性。112例患者中，分别有89例（80%）和80例（72%）成功测定了LI和TS。我们探寻了动力学参数与一些病理和临床参数之间的相关性。在34例接受统一缓解诱导和维持治疗的急性非淋巴细胞白血病患者中，通过Tpot和FTR测量的增殖活性，反应性患者高于无反应患者，缓解期超过8个月的患者高于缓解期较短的患者。进展期胃癌患者的增殖活性也高于疾病局限的患者。在胶质瘤患者中未发现动力学参数与临床和病理参数之间的相关性。这些数据表明，体内注射BUDR并结合FCM测量可在临床环境中进行，以便在相当大的患者系列中快速获得动力学数据。这可能会使动力学数据纳入旨在评估这些数据预后相关性的临床试验中。
