RESPONSE OF MAMMALIAN CELLS TO HALOGENATED PYRIMIDINES

当某些卤代嘧啶类化合物，如溴脱氧尿苷(BrdUrd)和 碘脱氧尿苷(IdUrd)被掺入细胞DNA，细胞变成 对电离辐射和化疗药物更敏感。这 多年来的观察导致了几项临床研究，最近 以评估肿瘤的选择性敏化是否可以 通过输注IdUrd，然后进行放射治疗。一个重要的问题 在这些研究中关于药物在多大程度上 被整合到细胞中。工作仍在继续，以开发量化技术 IdUrd掺入肿瘤和正常组织。IdUrd单抗 抗体在流式细胞术研究中被证明是有用的，以准确预测 标记指数(S期细胞比例)和实验室 目前参与(临床IdUrd研究)评估这一点 潜在的重要临床参数。我们已经做了活组织检查 资料来自至少10名接受过长期宫内节育器的患者 静脉输液。到目前为止，我们的发现是，替代 在大多数ALL患者中，伴有IUdR的胸腺嘧啶核苷的比例相对较低 从1%到10%不等。然而，现在就就以下问题发表声明还为时过早 置换的程度与整体放射治疗结果相一致。 我们将继续从以下方面收集和评估IUdR更换数据 下一年的病人。重要的是观察到一个人 接受宫内节育器输注5天的患者 10%的患者对巨大的头颈部病变有戏剧性的完全反应。 IUdR抗体的使用和图像分析使我们能够评估每一个 患者对lUdR掺入的异质性感到担忧。我们有 自动执行此过程，以便可以确定标签 指数和来自整个组织切片的异质性的度量。在……里面 除了使用lUdR抗体外，我们还使用Ki-67抗体 这应该是对我们的研究的补充，给我们一个增长的估计 肿瘤的一小部分。

When certain halogenated pyrimidines such as bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd) are incorporated into cellular DNA, cells become more sensitive to ionizing radiation and chemotherapy drugs. This observation has led to several clinical studies over the years and recently at the NCI to evaluate whether selective sensitization of tumors could be achieved by IdUrd infusion followed by radiation. An important question arises in these studies regarding the extent to which the drug is incorporated into cells. Work continues to develop techniques to quantify IdUrd incorporation into tumor and normal tissues. The IdUrd monoclonal antibody has proven useful in flow cytometry studies to accurately predict the labeling index (proportion of cells in S phase) and the laboratory is currently involved (with the clinical IdUrd study) in assessing this potentially important clinical parameter. We have obtained biopsied material from at least 10 patients who have received protracted IUdR intravenous infusion. Our findings to date have been that the replacement of thymidine with IUdR has been relatively low from most all patients ranging from 1-10%. However, it is to early to make a statement regarding the extent of replacement with the overall radiotherapy treatment outcome. We will continue to collect and evaluate IUdR replacement data from patients over the next year. Of significance was the observation that one patient who had received a five day infusion of IUdR with a replacement of 10% had a dramatic complete response of a large bulky head and neck lesion. Use of the IUdR antibody and image analysis has enabled us to assess each patient with respect to the heterogeneity of lUdR incorporation. We have automated this process such that it is feasible to determine a labelling index and a measure of heterogeneity from an entire tissue section. In addition to use of the lUdR antibody we are also using the Ki-67 antibody which should complement our studies by giving us an estimate of the growth fraction of the tumor.