Semi-Automated Computational Assessment of Cancer Organoid Viability Using Rapid Live-Cell Microscopy.
Semi-Automated Computational Assessment of Cancer Organoid Viability Using Rapid Live-Cell Microscopy.
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DOI：
10.1177/11769351221100754
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发表时间：
2022
影响因子：
2
通讯作者：
Abdullah, Kalil G.
中科院分区：
文献类型：
--
作者：
Buehler, Joseph D.;Bird, Cylaina E.;Savani, Milan R.;Gattie, Lauren C.;Hicks, William H.;Levitt, Michael M.;El Shami, Mohamad;Hatanpaa, Kimmo J.;Richardson, Timothy E.;McBrayer, Samuel K.;Abdullah, Kalil G.
患者来源的癌症有机化合物的创建代表了临床前建模的关键进展，最近已被应用于各种人类实体肿瘤类型。然而，用于评估体内肿瘤组织治疗反应的传统方法不太适合于评估癌症有机化合物，因为它们是时间密集型的，涉及组织破坏。为了解决这个问题，我们建立了一套来自患者的三维胶质瘤有机物，对它们进行化疗和放射治疗，用无毒细胞染料对有机物进行染色，并使用一种名为“尖端成像”的快速激光扫描共聚焦显微镜方法对它们进行成像。然后，我们开发并测试了一种碎裂算法来量化有机物地形中的异质性，作为一种潜在的生存能力的替代标记。这种算法，SSDquant，提供了有机表面的三维可视化表示，并提供了距离导出的有机质心的和平方距离(SSD)的数值测量。我们测试了SSD评分是否与传统免疫组织化学衍生的细胞活性标记物(细胞性和切割的caspase3表达)相关，并通过线性回归分析观察到它们之间有统计学意义的相关性。我们的工作描述了一种定量的、非侵入性的方法来连续测量患者来源的癌症器官活性，从而为这些模型在癌症生物学和治疗研究中的应用开辟了新的途径。
The creation of patient-derived cancer organoids represents a key advance in preclinical modeling and has recently been applied to a variety of human solid tumor types. However, conventional methods used to assess in vivo tumor tissue treatment response are poorly suited for the evaluation of cancer organoids because they are time-intensive and involve tissue destruction. To address this issue, we established a suite of 3-dimensional patient-derived glioma organoids, treated them with chemoradiotherapy, stained organoids with non-toxic cell dyes, and imaged them using a rapid laser scanning confocal microscopy method termed “Apex Imaging.” We then developed and tested a fragmentation algorithm to quantify heterogeneity in the topography of the organoids as a potential surrogate marker of viability. This algorithm, SSDquant, provides a 3-dimensional visual representation of the organoid surface and a numerical measurement of the sum-squared distance (SSD) from the derived mass center of the organoid. We tested whether SSD scores correlate with traditional immunohistochemistry-derived cell viability markers (cellularity and cleaved caspase 3 expression) and observed statistically significant associations between them using linear regression analysis. Our work describes a quantitative, non-invasive approach for the serial measurement of patient-derived cancer organoid viability, thus opening new avenues for the application of these models to studies of cancer biology and therapy.
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影响因子：
--
作者：
Pernik MN;Bird CE;Traylor JI;Shi DD;Richardson TE;McBrayer SK;Abdullah KG
通讯作者：
Abdullah KG
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.4
作者：
Bolck, Hella A.;Corro, Claudia;Moch, Holger
通讯作者：
Moch, Holger
影响因子：
64.5
作者：
Jacob F;Salinas RD;Zhang DY;Nguyen PTT;Schnoll JG;Wong SZH;Thokala R;Sheikh S;Saxena D;Prokop S;Liu DA;Qian X;Petrov D;Lucas T;Chen HI;Dorsey JF;Christian KM;Binder ZA;Nasrallah M;Brem S;O'Rourke DM;Ming GL;Song H
通讯作者：
Song H
影响因子：
5.8
作者：
Legland, David;Arganda-Carreras, Ignacio;Andrey, Philippe
通讯作者：
Andrey, Philippe