Use of the in vivo hollow fiber assay in natural products anticancer drug discovery.

Use of the in vivo hollow fiber assay in natural products anticancer drug discovery.
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DOI:
10.1021/np800767a
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发表时间:
2009-03-27
影响因子:
5.1
通讯作者:
Swanson, Steven M.
Swanson, Steven M.
中科院分区:
生物学2区
文献类型:
--
作者:
Mi, Qiuwen;Pezzuto, John M.;Farnsworth, Norman R.;Wani, Mansukh C.;Kinghorn, A. Douglas;Swanson, Steven M.

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体内中空纤维试验是由美国国家癌症研究所(NCI)开发的,旨在帮助弥合基于细胞的体外分析与在免疫缺陷小鼠中繁殖的人类肿瘤模型之间的差距。他们的目标是开发一种中间检测方法,帮助预测在60个细胞系中发现的活性化合物在随后的异种移植系统中将具有活性。这是必要的,因为传统的异种移植分析在所需动物数量、完成分析所需的时间和必要的财政承诺方面成本很高。为了解决这个问题,NCI开发治疗计划的研究人员设计了一种方法,在惰性中空纤维中繁殖人类癌细胞,这些纤维的孔小到足以保留癌细胞,但大到足以允许潜在的化疗药物进入,包括大的蛋白质和其他重要物质。含有增殖癌细胞的纤维被移植到腹膜或皮下,宿主小鼠被用测试剂治疗,随后这些纤维被提取用于分析活细胞团。该测试已经成功地帮助来自世界各地的研究人员,包括我们自己的研究小组,优先考虑在体外活跃的化合物,以便在传统的异种移植系统中进行进一步测试。
The in vivo hollow fiber assay was developed at the National Cancer Institute (NCI) to help bridge the gap between in vitro cell-based assays and human tumor models propagated in immunodeficient mice. The goal was to develop an intermediate assay that could help predict which compounds found active in the 60-cell line panel would be active in a subsequent xenograft system. This was necessary due to the high cost of the traditional xenograft assay in terms of number of animals required, time for assay completion, and financial commitment necessary. To address this problem, investigators of the NCI Developmental Therapeutics Program designed a method of propagating human cancer cells in inert hollow fibers with pores small enough to retain the cancer cells but large enough to permit entry of potential chemotherapeutic drugs, including large proteins and other important substances. Fibers containing proliferating cancer cells are transplanted into the peritoneum or under the skin, the host mice are treated with a test agent and the fibers are subsequently retrieved for analysis of viable cell mass. The assay has been successful in helping investigators from around the world, including our own research group, prioritize compounds active in vitro for further testing in the traditional xenograft system.
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