Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response.
Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response.
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DOI：
10.1097/mpa.0000000000000543
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发表时间：
2016-07
期刊：
影响因子：
2.9
通讯作者：
Skala MC
中科院分区：
文献类型：
--
作者：
Walsh AJ;Castellanos JA;Nagathihalli NS;Merchant NB;Skala MC
来自原发性胰腺导管腺癌的三维类器官是在患者特异性组织上测试潜在抗癌药物的一个有吸引力的平台。光学代谢成像（OMI）是一种用于评估药物引起的细胞代谢变化的新工具，其定量终点（OMI指数）被评估为胰腺癌类器官药物反应的生物标志物。光学代谢成像用于评估原发性小鼠和人类胰腺癌类器官中的恶性细胞和成纤维细胞药物反应。抗癌药物可显着降低小鼠和人类胰腺癌类器官的 OMI 指数。 OMI 数据的亚群分析揭示了异质性药物反应，并阐明了 7 天时间过程中有反应和无反应的细胞群。光学代谢成像指数与细胞增殖和细胞死亡的免疫荧光检测显着相关。原发性胰腺导管腺癌类器官的光学代谢成像对药物引起的代谢变化高度敏感，为监测动态药物反应提供了一种无损方法，并为患者特异性药物测试和药物开发提供了一个新平台。
Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on patient-specific tissue. Optical metabolic imaging (OMI) is a novel tool used to assess drug-induced changes in cellular metabolism, and its quantitative end point, the OMI index, is evaluated as a biomarker of drug response in pancreatic cancer organoids. Optical metabolic imaging is used to assess both malignant cell and fibroblast drug response within primary murine and human pancreatic cancer organoids. Anticancer drugs induce significant reductions in the OMI index of murine and human pancreatic cancer organoids. Subpopulation analysis of OMI data revealed heterogeneous drug response and elucidated responding and nonresponding cell populations for a 7-day time course. Optical metabolic imaging index significantly correlates with immunofluorescence detection of cell proliferation and cell death. Optical metabolic imaging of primary pancreatic ductal adenocarcinoma organoids is highly sensitive to drug-induced metabolic changes, provides a nondestructive method for monitoring dynamic drug response, and presents a novel platform for patient-specific drug testing and drug development.