Abstract:
:Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests. The obtained image data were thresholded using a local entropy filter after which the image foreground was split into local regions, for a supervised classification into tumor or fibroblast cell types. Robust statistical methods were applied to evaluate treatment effects on growth and morphology. Both novel and existing computational approaches were compared at each step, while prioritizing high experimental throughput. Docetaxel was found to be the most effective drug that blocked both tumor growth and invasion. These effects were also validated in PDX tumors in vivo. Our research opens new avenues for high-content drug screening based on patient-derived cell cultures, and for personalized chemosensitivity testing.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Ahonen I,Åkerfelt M,Toriseva M,Oswald E,Schüler J,Nees Mdoi
10.1038/s41598-017-06544-xsubject
Has Abstractpub_date
2017-07-26 00:00:00pages
6600issue
1issn
2045-2322pii
10.1038/s41598-017-06544-xjournal_volume
7pub_type
杂志文章abstract::Parasitism is a successful survival strategy across all kingdoms and has evolved repeatedly in angiosperms. Parasitic plants obtain nutrients from other plants and some are agricultural pests. Obligate parasites, which cannot complete their lifecycle without a host, may lack functional photosystems (holoparasites), or...
journal_title:Scientific reports
pub_type: 杂志文章
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更新日期:2015-12-02 00:00:00
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journal_title:Scientific reports
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journal_title:Scientific reports
pub_type: 杂志文章
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journal_title:Scientific reports
pub_type: 杂志文章
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更新日期:2018-06-19 00:00:00
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journal_title:Scientific reports
pub_type: 已发布勘误
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05694
更新日期:2014-07-16 00:00:00
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pub_type: 杂志文章
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journal_title:Scientific reports
pub_type: 杂志文章
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更新日期:2018-07-26 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
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更新日期:2018-02-19 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01397
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pub_type: 杂志文章
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journal_title:Scientific reports
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2014-12-12 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
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journal_title:Scientific reports
pub_type: 杂志文章,meta分析
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更新日期:2017-09-06 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-79722-z
更新日期:2021-01-12 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
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更新日期:2020-10-22 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep26145
更新日期:2016-05-17 00:00:00
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journal_title:Scientific reports
pub_type: 杂志文章
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更新日期:2017-01-10 00:00:00
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pub_type: 杂志文章
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