RESPONSE OF MAMMALIAN CELLS TO HALOGENATED PYRIMIDINES

当某些卤代嘧啶如溴脱氧尿苷（BrdUrd）和 碘脱氧尿苷（IdUrd）被掺入细胞DNA中，细胞变得 对电离辐射和化疗药物更敏感。这 多年来， 在NCI评估是否可以选择性致敏肿瘤， 通过IdUrd输注随后进行辐射来实现。一个重要的问题 在这些研究中出现了关于药物 整合到细胞中。工作继续发展技术， IdUrd掺入肿瘤和正常组织。IdUrd单克隆抗体 已证明抗体在流式细胞术研究中可用于准确预测 标记指数（S期细胞的比例）和实验室检查为 目前参与（临床IdUrd研究）评估这一点 潜在的重要临床参数。我们已经取得了 来自至少10名接受长期IUdR的患者的材料 静脉输液到目前为止，我们的发现是， 在大多数患者中， 范围为1 - 10%。然而，现在就发表声明还为时过早， 替代的程度与整体放疗治疗结果有关。 我们将继续收集和评估IUdR替代数据， 明年的病人。重要的是观察到， 一名患者接受了为期5天的IUdR输注， 10%有一个巨大的笨重的头部和颈部病变的戏剧性的完全反应。 使用IUdR抗体和图像分析使我们能够评估每个 患者的lUdR掺入的异质性。我们有 使该过程自动化，以便可以确定标签 指数和来自整个组织切片的异质性的量度。在 除了使用lUdR抗体外，我们还使用Ki-67抗体 这应该可以补充我们的研究， 肿瘤的一部分。

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.