Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening
Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening
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DOI：
10.1016/j.jim.2004.06.003
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发表时间：
2004-09-01
影响因子：
2.2
通讯作者：
Smith, C
中科院分区：
文献类型：
--
作者：
Gasparetto, M;Gentry, T;Smith, C
在这份报告中，我们描述了一种新的流式细胞术技术，称为流式细胞术高含量筛选（FC-HCS），它涉及半自动化处理和分析的多参数流式细胞术样本。作为FC-HCS技术的第一个测试，我们用它来筛选2000个化合物库，称为国家癌症研究所（NCI）多样性集，以确定能够增强治疗性单克隆抗体利妥昔单抗抗抗抗淋巴瘤活性的药物。FC-HCS从多样性组中鉴定出15种化合物，这些化合物显著增强利妥昔单抗抑制淋巴瘤细胞中细胞周期进展和诱导细胞凋亡的能力。使用细胞增殖、细胞凋亡和细胞生长的附加测定法证实了几种化合物筛选结果的有效性。FC-HCS技术相对简单可靠，在单个流式细胞仪上每天可处理多达1000个样本。FC-HCS技术可用于多种应用，包括药物发现、患者的免疫学监测、功能基因组学研究和组织工程努力。(C)2004 Elsevier B. V.保留所有权利。
In this report, we describe a new flow cytometry technique termed flow cytometric high-content screening (FC-HCS) which involves semi-automated processing and analysis of multiparameter flow cytometry samples. As a first test of the FC-HCS technique, we used it to screen a 2000-compound library, called the National Cancer Institute (NCI) Diversity Set, to identify agents that would enhance the anti-lymphoma activity of the therapeutic monoclonal antibody rituximab. FC-HCS identified 15 compounds from the Diversity Set that significantly enhanced the ability of rituximab to inhibit cell cycle progression and induce apoptosis in lymphoma cells. The validity of the screening results was confirmed for several compounds using additional assays of cell proliferation, apoptosis and cell growth. The FC-HCS technique was relatively simple and reliable and could process up to 1000 samples/day on a single flow cytometer. The FC-HCS technique may be useful for a variety of applications including drug discovery, immunologic monitoring of patients, functional genomics studies and tissue engineering efforts. (C) 2004 Elsevier B.V. All rights reserved.