MCF10DCIS.com as a preclinical chemopreventive screen

我们的目的是验证临床前异种移植模型，用于评估化学试剂改变原位乳腺癌中替代终点生物标志物（SEB）表达的能力。 我们已经开发了一种人乳腺上皮细胞系，MCF10DCIS.com，它产生粉刺型原位导管癌。在将1 × 10/7细胞的Matrigel注射到免疫缺陷小鼠中后6-8周获得近1克组织。我们将能够通过与Karmanos癌症研究所进行的临床研究结果直接比较来验证模型的结果，在该研究中，诊断为DCIS的患者在手术前三周每天服用100 mg大豆异黄酮。分析手术标本中包括连接蛋白43、p21、bax、bcl-2、p21和CDK 5在内的许多标志物的表达。然而，临床前模型允许我们用化学预防剂治疗异种移植小鼠组，并在多个时间间隔而不是临床研究中可能的单个时间点确定治疗和未治疗的病变中生物标志物的表达。我们还将能够测试其他化学预防剂，剂量和组合。异种移植病变的大小将使我们能够研究化学预防剂，剂量和组合。异种移植物病变的大小将使我们能够在治疗前后观察许多额外的生物标志物，而不是可能从临床标本中获得的稀疏材料。一旦得到验证，MCF10DCIS.com将提供一个独特的原位人导管癌异种移植模型，用于快速筛选推定的化学预防剂。与MCF 10AT 1原位结合用于快速筛选推定的化学预防剂。与进行性癌前乳腺疾病的MCF 10AT 1异种移植模型组合，该模型还将提供验证不同SEB用于筛选化学预防剂的相关性的手段。

Our objective is to validate a preclinical xenograft model for assessment of the ability of chemical agents to alter surrogate end- point biomarker (SEB) expression in breast carcinoma in situ. We have developed a human breast epithelial cell line, MCF10DCIS.com, which produces ductal carcinoma in situ of the comedo type. Nearly one gram of tissue is obtained 6-8 weeks after injecting 1x10/7 cells in Matrigel into immune deficient mice. We will be able to validate results with the model by direct comparison with results of a clinical study being conducted at the Karmanos Cancer Institute in which patients diagnosed with DCIS are given 100 mg of soy isoflavones daily for three weeks prior to surgery. Surgical specimens are analyzed for expression of a number of markers including connexin 43, p21, bax, bcl-2, p21, and CDK5. However, the preclinical model allows us to treat groups of xenografted mice with chemopreventive agents and determine expression of biomarkers in lesions from treated and untreated at multiple intervals rather than the single time point possible in the clinical study. We will also be able to test additional chemopreventive agents, doses, and combinations. The size of the xenograft lesions will allow us to look at chemopreventive agents, doses, and combinations. The size of the xenograft lesions will allow us to look at many additional biomarkers, both before and after treatment, than the sparse material likely to be available from the clinical specimens. Once validated, MCF10DCIS.com will provide a unique xenograft model of human ductal carcinoma in situ for rapid screening of putative chemopreventive agents. In combination with the MCF10AT1 in situ for rapid screening of putative chemopreventive agents. In combination with the MCF10AT1 xenograft model of progressive premalignant breast disease, the model will also provide a means of validating the relevance of different SEBs for screening chemopreventive agents.