Name: quantifying the brain metastatic tumor micro-environment using an organ-on-a chip 3d model, machine learning, and confocal tomography
Uploaded: 2020-08-16T15:00:00
Description: Watch this Scientific Journal Video about Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography at JoVE.com

我们感谢国家癌症研究所的斯蒂格实验室慷慨捐赠MDA-MB-231-BR-GFP细胞。在密歇根大学生物接口研究所（BI）进行了共生显微镜。在密歇根大学流细胞学核心进行流细胞学。病毒载体是由密歇根大学病媒核心创建。我们还感谢凯利·基德威尔对这些数据的统计分析提供指导。
资金：
C.R.O.部分得到国家卫生和三十二培训研究金（T32CA009676）和1R21CA245597-01的支助。T.M.W. 部分得到 1R21CA245597-01 和国家卫生研究院国家促进转化科学中心的支持，奖励编号为 UL1TR002240。国家卫生研究院国家癌症研究所根据奖号1R21CA245597-01、P30CA046592、5T32CA009676-23、CA196018、AI116482、METAvivor基金会和乳腺癌研究基金会提供了材料和表征的资助。内容完全由作者负责，不一定代表国家卫生研究院的官方观点

1. 准备血脑屏障利基模具
注：这个平台中使用的培养设备是基于PDMS的脚手架，我们建立一个细胞血脑屏障利基。它由两部分由多孔膜隔开。准备血脑屏障利基两个SU-8模具使用光刻是必要的26，27。26,将首先为100μm厚的模具描述协议，然后为200μm厚的模具提供注释。
<ol><li>要准备模具，请用丙酮用挤压瓶清洁 4 英寸硅片，然后用氮?...

<ol>
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我们开发并提出了一种新方法，可以调整临床成像分析中经常使用的工具，以测量癌细胞通过内皮屏障进入脑组织外创和迁移。我们认为这种方法对体内和体外测量都很有用;我们已经证明了它在3D微流体系统上重新验证脑血管的用途。癌细胞测量，包括距离外创，体积外创百分比，球面和体积使用这种技术进行量化。距离外在和体积外加百分比允许用户重建芯片中癌细胞的位置，以评估跨越屏障?...

脑转移是最致命的癌症病变;10-30%的癌症转移至大脑，平均存活期只有+5-20个月，取决于癌症类型,1，2。研究癌症转移时出现的一个主要问题是亚克隆如何从血液的幽默环境迁移到大脑3、4,等器官。这个问题导致了许多迁移、入侵和外向分析的变体。所有这些方法都共享计数或测量细胞属性的关键步骤，这些细胞会根据刺激从一个位置移动到另一个位置。大多数现成的迁移测定都用于研究癌细胞的二维（2D）迁移。这些都阐明了丰富的知识;然而，它们并没有概括体内系统的三维性质，其他方法可以提供5。因此，有必要研究三维（3D）系统中的肿瘤微环境（TME），但可用于三维结构的分析方法有限，而且往往不一致。
最流行的3D工具之一是博伊登腔室，它由悬浮在井底的膜组成，将两个不同的区域隔开。博伊登介绍了研究白细胞化疗的测定方法。底部区域可以通过化学或其他方法6、7,来变化，以诱导上部区域的细胞迁移到下部区域。量化迁移的细胞数的最常见方法是使用缓冲液从膜底部释放细胞，对它们进行解，然后根据溶液7中的DNA含量量进行计数。这种间接方法由于技术变异性而容易出现操作者错误，该过程会破坏有关癌症表型和微环境的信息。博伊登腔室测定的变化涉及固定留在膜上的迁徙细胞，但只提供不再可行的细胞计数，以继续研究6，8，9。,8,9
由于博伊登腔室的局限性和微流体社区创新的增长，迁移测定芯片已经开发出来，观察细胞的运动，以响应一个方向的刺激，而不是三个10，11，12。,11,12这些迁移测定有助于控制诸如流动或单细胞分离等因子13、14，14从而更好地解释结果;13然而，它们的2D格式不可避免地会丢失一些动态信息。最近的研究集中在3D环境中的外在（即细胞从循环运动到组织，如血脑屏障）14，15。,15与使用博伊登腔室或2D微流体迁移装置16收集的测量结果，在细胞屏障/膜上发生的组织外向距离和探测行为更为精细。因此，能够对 3D 外创进行适当成像和分析的设备对于捕获这些复杂的测量值至关重要，但缺乏文献。
独立于迁移测定，已经开发出强大的成像技术，用于磁共振成像（MRI）和断层扫描，能够识别和准确地重建组织在3D空间17，18。,18这些技术根据组织的属性获取 z 堆栈中的图像和分割部分图像，然后将分割的图像转换为三维网格 19、20、21。19,20,21这使得医生能够可视化在3D个别器官，骨骼和血管，以帮助手术规划或协助诊断癌症或心脏病22，23。22,在这里，我们将展示这些方法可以适用于显微标本和3D外创装置。
为此，我们开发了创新的共声断层扫描技术，该技术提供了灵活性，通过调整现有的断层扫描工具，研究肿瘤细胞在膜上外向。这种方法能够研究癌细胞行为与细胞屏障（如内皮细胞层）相互作用时的全部范围。癌细胞表现出探测行为;有些可能入侵，但保持接近膜，而其他人很容易穿过屏障。这项技术能够产生关于细胞在所有维度24中的表型的信息。与更复杂的体内穆林模型相比，使用这种方法研究TME既相对便宜，易于解释，又可重复。提出的方法应该为通过适应肿瘤区域来研究许多类型的肿瘤和微环境提供强有力的基础。
我们描述并演示了3D微流体血脑利基（μmBBN）平台（图1），其中屏障和利基的关键元素（脑微血管内皮细胞和星形细胞）可以培养一个较长的时间（大约9天），由共和显微镜荧光成像，并使用我们的共体断层扫描技术重建的图像（图2）;都旨在以可重复和定量的方式了解微转移的发展以及肿瘤微环境的变化。血脑屏障与大脑利基的界面由脑微血管内皮细胞组成，这些细胞通过地下室膜、星形细胞脚和百分细胞25加强。我们选择性地关注星细胞和内皮成分，因为它们在血脑屏障的形成和调节中的重要性。我们演示如何利用这个平台制造、播种、图像和分析癌细胞和肿瘤微环境细胞和体液成分。最后，我们展示如何使用机器学习来识别能够通过模型μmBBN传递的癌细胞的内在表型差异，并赋予它们大脑转移电位24的客观索引。此方法生成的数据集可用于回答有关转移、治疗策略和 TME 在这两者中的作用的基本和转化问题。

<table>
	<tbody>
		<tr>
			<td>0.25% Trypsin-EDTA with phenol red</td>
			<td>Thermo Fisher Scientific</td>
			<td>25200056</td>
			<td></td>
		</tr>
		<tr>
			<td>1.5 mm biopsy punch with plunger</td>
			<td>Integra LifeSciences Corporation</td>
			<td>33-31A-P/25</td>
			<td></td>
		</tr>
		<tr>
			<td>10x MEM</td>
			<td>Thermo Fisher Scientific</td>
			<td>11430030</td>
			<td></td>
		</tr>
		<tr>
			<td>150 mm petri dishes</td>
			<td>Fisher Scientific</td>
			<td>FB0875714</td>
			<td></td>
		</tr>
		<tr>
			<td>1x DPBS, without Ca and Mg</td>
			<td>Thermo Fisher Scientific</td>
			<td>14190144</td>
			<td></td>
		</tr>
		<tr>
			<td>200uL pipette tip</td>
			<td>Fisher Scientific</td>
			<td>02-707-411</td>
			<td></td>
		</tr>
		<tr>
			<td>4 inch silicon wafer</td>
			<td>University Wafer</td>
			<td>452</td>
			<td></td>
		</tr>
		<tr>
			<td>48 mm wide packing tape</td>
			<td>Fisher Scientific</td>
			<td>19-072-097</td>
			<td></td>
		</tr>
		<tr>
			<td>50 x 75 mm glass slide</td>
			<td>Fisher Scientific</td>
			<td>12-550C</td>
			<td></td>
		</tr>
		<tr>
			<td>A1 confocal microscope</td>
			<td>Nikon</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>acetone</td>
			<td>Fisher Scientific</td>
			<td>A9-20</td>
			<td></td>
		</tr>
		<tr>
			<td>antibiotic/antimycotic (penicillin/streptomycin/amphotericin)</td>
			<td>Gibco</td>
			<td>15240062</td>
			<td></td>
		</tr>
		<tr>
			<td>box cutter blade</td>
			<td>Fisher Scientific</td>
			<td>NC1721575</td>
			<td></td>
		</tr>
		<tr>
			<td>dissection scissors</td>
			<td>Fisher Scientific</td>
			<td>08-951-5</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM with 4.5 g/L glucose</td>
			<td>Thermo Fisher Scientific</td>
			<td>11960-044</td>
			<td></td>
		</tr>
		<tr>
			<td>double sided tape</td>
			<td>Fisher Scientific</td>
			<td>NC0879005</td>
			<td></td>
		</tr>
		<tr>
			<td>EGM-2</td>
			<td>Lonza</td>
			<td>CC-3162</td>
			<td></td>
		</tr>
		<tr>
			<td>Fetal Bovine Serum, Heat inactivated</td>
			<td>Corning</td>
			<td>MT35011CV</td>
			<td></td>
		</tr>
		<tr>
			<td>Fiji software</td>
			<td>ImageJ</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>glass vial</td>
			<td>Fisher Scientific</td>
			<td>03-341-25D</td>
			<td></td>
		</tr>
		<tr>
			<td>glutamax</td>
			<td>Thermo Fisher Scientific</td>
			<td>35050061</td>
			<td></td>
		</tr>
		<tr>
			<td>hCMEC/D3</td>
			<td>EMD Millipore</td>
			<td>SCC066</td>
			<td></td>
		</tr>
		<tr>
			<td>Jupyter notebook</td>
			<td>Anaconda</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>L-glutamine</td>
			<td>Thermo Fisher Scientific</td>
			<td>25030081</td>
			<td></td>
		</tr>
		<tr>
			<td>Matrigel - growth factor reduced with phenol red</td>
			<td>Corning</td>
			<td>CB-40230A</td>
			<td></td>
		</tr>
		<tr>
			<td>MDA-MB-231</td>
			<td>ATCC</td>
			<td>HTB-26</td>
			<td></td>
		</tr>
		<tr>
			<td>MDA-MB-231-BR-GFP</td>
			<td>Dr. Patricia Steeg, NIH</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>N-2 growth supplement</td>
			<td>Thermo Fisher Scientific</td>
			<td>17502048</td>
			<td></td>
		</tr>
		<tr>
			<td>normal human astrocytes (NHA)</td>
			<td>Lonza</td>
			<td>CC-2565</td>
			<td></td>
		</tr>
		<tr>
			<td>Orange software</td>
			<td>University of Ljubljana</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Pasteur pipette</td>
			<td>Fisher Scientific</td>
			<td>13-711-9AM</td>
			<td></td>
		</tr>
		<tr>
			<td>Photolithography masks</td>
			<td>Photosciences Incorporated</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>pLL3.7-dsRed</td>
			<td>University of Michigan Vector Core</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>pLL-EV-GFP</td>
			<td>University of Michigan Vector Core</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>pLOX-TERT-iresTK</td>
			<td>Addgene</td>
			<td>12245</td>
			<td></td>
		</tr>
		<tr>
			<td>pMD2.G</td>
			<td>Addgene</td>
			<td>12259</td>
			<td></td>
		</tr>
		<tr>
			<td>polycarbonate membrane, 5um pore size</td>
			<td>Millipore</td>
			<td>TMTP04700</td>
			<td></td>
		</tr>
		<tr>
			<td>psPAX2</td>
			<td>Addgene</td>
			<td>12260</td>
			<td></td>
		</tr>
		<tr>
			<td>PureCol, 3 mg/mL</td>
			<td>Advanced Biomatrix</td>
			<td>5005</td>
			<td>Type I bovine collagen</td>
		</tr>
		<tr>
			<td>sodium bicarbonate</td>
			<td>Thermo Fisher Scientific</td>
			<td>25080094</td>
			<td></td>
		</tr>
		<tr>
			<td>sodium pyruvate</td>
			<td>Thermo Fisher Scientific</td>
			<td>11360070</td>
			<td></td>
		</tr>
		<tr>
			<td>Solo cup</td>
			<td>Fisher Scientific</td>
			<td>NC1416545</td>
			<td></td>
		</tr>
		<tr>
			<td>SU-8 2075</td>
			<td>MicroChem Corporation</td>
			<td>Y111074 0500L1GL</td>
			<td></td>
		</tr>
		<tr>
			<td>SU8 developer</td>
			<td>MicroChem Corporation</td>
			<td>Y020100 4000L1PE</td>
			<td></td>
		</tr>
		<tr>
			<td>Sylgard 184</td>
			<td>Ellsworth Adhesive Company</td>
			<td>NC0162601</td>
			<td></td>
		</tr>
		<tr>
			<td>Toluene</td>
			<td>Sigma-Aldrich</td>
			<td>179965-1L</td>
			<td></td>
		</tr>
		<tr>
			<td>Tricholoro perfluoro octyl silane</td>
			<td>Sigma-Aldrich</td>
			<td>448931-10G</td>
			<td></td>
		</tr>
	</tbody>
</table>

quantifying the brain metastatic tumor micro-environment using an organ-on-a chip 3d model, machine learning, and confocal tomography

脑转移是最致命的癌症病变;10-30%的癌症转移至大脑，平均存活期只有+5-20个月，取决于癌症类型。为了减少大脑转移性肿瘤负担，需要解决基本和转化知识方面的差距。主要挑战包括缺乏可重复的临床前模型和相关工具。脑转移的三维模型可以生成相关的分子和表型数据，用于满足这些需求，结合专用分析工具。此外，与穆林模型相比，患者肿瘤细胞穿过血脑屏障进入大脑微环境的细胞器官模型产生快速的结果，并且更可解释定量方法，从而适合高通量测试。在这里，我们描述并演示了一种新的3D微流体血脑利基（μmBBN）平台的使用，其中利基的多个元素可以培养很长一段时间（几天），荧光成像由共和显微镜，并使用创新的共体断层扫描技术重建的图像;所有旨在了解微转移的发展以及肿瘤微环境（TME）的变化，以可重复和定量的方式。我们演示如何使用这个平台制造、播种、图像和分析癌细胞和 TME 细胞和体液成分。此外，我们展示人工智能 （AI） 如何用于识别能够通过模型 μmBBN 传递的癌细胞的内在表型差异，并为它们分配一个脑转移潜力的客观索引。此方法生成的数据集可用于回答有关转移、治疗策略的疗效以及 TME 在两者中的作用的基本和转化问题。

利用这种技术，我们分析了标有不同荧光蛋白或染料的细胞类型。我们演示了使用使用 μmBBN 芯片与 hCMEC/D3-DSRed 和非荧光星形细胞一起使用这种方法。脑微血管内皮细胞被播种到多孔膜（5μm轨道蚀刻毛孔），并在37°C下放置在37°C低于5%CO 2的培养箱34中。三天后，通过显微镜确认内皮层的汇合，然后将癌细胞放置在内皮层的顶部。两个乳腺癌细胞系，一个称为MDA-MB-231-BR-GF...

Watch this Scientific Journal Video about Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography at JoVE.com

Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography

在这里，我们提出了一个协议，用于准备和培养血脑屏障转移肿瘤微环境，然后使用共体成像和人工智能（机器学习）量化其状态。

使用有机体片 3D 模型、机器学习和共声断层扫描量化脑转移肿瘤微环境

Brain metastases are the most lethal cancer lesions; 10-30% of all cancers metastasize to the brain, with a median survival of only ~5-20 months, ...

共声断层扫描被开发为获得癌细胞行为的全部范围，因为它们与细胞屏障和利基相互作用。此方法为研究转移发生时的转移提供了基础。此方法可用于量化活细胞行为。当与机器学习相结合时，共声断层扫描可用于各种芯片上的器官平台。分析原发性或复发性肿瘤或循环肿瘤细胞可以构成预测大脑转移和从非脑转移细胞中辨别大脑转移的重要诊断工具。要组装微流体 BBN 器件，请将设备从真空干燥器传输到适当的表面上，入口朝下，将整个装置放入等离子室。将整个设置放入等离子室中，然后拉真空，然后以 80 瓦的等离子处理设备 30 秒。在治疗结束时，使用导轨快速放置设备，入口侧上放在实验室工作台上的玻璃幻灯片上，在设备的 PDM 和幻灯片之间形成永久的粘合。接下来，插入 200 微升移液器尖端，从尖端切入所有入口和插座 2 毫米，并将设备放入等离子室中，进行 8 分钟、200 瓦的等离子处理。设备冷却后，将设备放入无菌二次容器中，并在质粒处理后 15 分钟内，通过底部室的移液器尖端将 120 微升胶原蛋白星细胞溶液转移到设备中。让溶液穿过腔室进入相反的移液器尖端，并填充设备的下一个通道。当设备的所有四个通道都已填充时，将芯片放在细胞培养箱中一小时。当胶原蛋白设置时，用适当的完整细胞培养基为底部腔室喂气，并在完整的内皮介质中涂上2%的生长因子，减少母细胞。两个腔室编码后，将设备放入培养箱一小时，然后用适当的介质冲洗上腔室。交替提示，见30微升的1倍10至第六内皮细胞每毫升适当的介质，通过尖端进入上室每15分钟，每个尖端共4个等同细胞。在种子之间孵育设备。当所有内皮细胞都播种后，用培养物填充所有提示，然后将设备返回到细胞培养箱 48 小时。当内皮层成熟时，更换芯片中的培养介质以补充细胞培养介质，并给每个顶室通道播种30微升，每毫升10倍至6个癌细胞的适当介质。每个 30 微升的细胞等同物播种后，将设备返回孵化器 15 分钟，然后用适当的介质填充所有提示，将设备返回细胞培养箱 24 至 48 小时。设备进行培养和成像后，测量癌细胞的表型，打开提供的软件，将共体图像读入内存。该软件会将每个颜色通道从 3D 共和图像保存到一个单独的 TIFF 文件中。选择"更改每个显微镜通道的不透明度值"，并调整图像中颜色通道的通道 Alpha 值，以便移除背景，并且仅保留单元格中的荧光。要可视化效果，请选择"查看 3D 渲染"以验证阈值是否设置正确，如果图像看起来正确，请在实验跟踪器电子表格中保存不透明度值。然后，使用行进立方体将卷图像转换为以 VTK 数据格式保存的单个 3D 三角形网格化对象。要将平面拟合到内皮屏障，请首先定位细胞质心。使用多数据连接筛选器通过 VTK 文件中的网格列表迭代，以提取未连接的区域。计算每个网格的质心，并将测量添加到对太大或太小的网格进行重心筛选的列表。要将平面拟合内皮细胞的质心列表，请使用误差最小化方法，运行可视化 RFP 质心和平面拟合，以生成和绘制平面拟合，并检查平面的拟合，并相应地手动调整拟合。正确安装平面后，将平面的法线保存到实验跟踪器文件中。要用平面测量内皮层特征后的每个癌细胞表型，加载细胞分析功能并在实验跟踪器信息中运行 Read，并分析存在的通道"以迭代和分析VTK文件中的每个区域。对于每个区域，函数将剪辑每个单元格，以便计算膜下方的网格。要测量细胞表型，请计算每个癌细胞的形状、体积和位置。然后测量每个被切断的癌细胞的体积和位置，以计算通过内皮屏障外创的细胞的百分比。对多个实验执行这些步骤后，运行导出数据作为单个 xlsx 文件'，以将数据保存在电子表格中。具有汇合内皮屏障的微流体BBN芯片在实验中是可以接受的，而具有特别差内皮覆盖率的微流体BBN芯片则不能。在这个代表性分析中，寻求癌细胞系的大脑，表现出一种细胞的亚群，这些细胞在内皮屏障中外泄，并深入到微流体BBN芯片的大脑利基空间。 在暴露后两天和九天，父母癌细胞在远离大脑利基空间的屏障上保持了相当一部分细胞，而脑转移癌细胞群体保持一个大于100%的细胞比例外创。癌细胞形状的形态定量表明，父母细胞在播种后第一天表现出的球形细胞较少，而经过两天和九天的相互作用，两个癌细胞系都趋向于降低球面性。此外，与癌细胞相比，在进入胃膜利基的癌细胞亚细胞数量较小，而癌细胞在不外泄进入大脑的情况下与内皮屏障保持相互作用。寻求癌细胞系和患者衍生的异种移植物，在微流体BBN芯片中表现出一种表型模式，可以通过机器学习来区分大脑转移和非脑转移癌细胞。自我选择很重要。通道数较高的内皮细胞表现出可变屏障行为。此外，癌细胞及其荧光表达可能会随着时间而变化。在这个程序之后，研究人员可以采用分子分析的秘密的家或细胞在设备，以研究转移的分子机制。该技术通过将工程微环境与利基成分的定量成像相结合，探索癌细胞与其微环境之间的复杂相互作用。

Research

JoVE Journal

Cancer Research

The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics

The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics

该<em&gt;果蝇</em&gt;成虫盘瘤模型：基因的表达与肿瘤侵袭性的可视化和定量遗传马赛克

Drosophila melanogaster has emerged as a powerful experimental system for functional and mechanistic studies of tumor development and progression in the ...

科研

癌症研究

Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

肝大肠癌转移的高级动物模型：成像技术和转移性克隆性质

Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches1,2. ...

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues

肿瘤组织中高通量芯片测序的染色质状态全基因组图谱集成平台

Histone modifications constitute a major component of the epigenome and play important regulatory roles in determining the transcriptional status of ...

Native Chromatin Immunoprecipitation Using Murine Brain Tumor Neurospheres

利用小鼠脑肿瘤球的原发染色质沉淀

Epigenetic modifications may be involved in the development and progression of glioma. Changes in methylation and acetylation of promoters and regulatory ...

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts

超声引导组织定向细胞植入术在生物学相关转移性肿瘤移植中的应用

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard ...

Live-Cell Imaging Assays to Study Glioblastoma Brain Tumor Stem Cell Migration and Invasion

活体细胞成像技术研究胶质瘤脑干细胞的迁移和侵袭

Glioblastoma (GBM) is an aggressive brain tumor that is poorly controlled with the currently available treatment options. Key features of GBMs include ...

Digital Polymerase Chain Reaction Assay for the Genetic Variation in a Sporadic Familial Adenomatous Polyposis Patient Using the Chip-in-a-tube Format

数字聚合酶链反应法测定零星家族性腺瘤性息肉病患者的基因变异

The quantitative analysis of human genetic variation is crucial for understanding the molecular characteristics of serious medical conditions, such as ...

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

肿瘤治疗胶质母细胞瘤的临床应用

Glioblastoma is the most common and lethal form of brain cancer, with a median survival of 15 months after diagnosis and a 5 year survival rate of only 5% ...

Longitudinal Morphological and Physiological Monitoring of Three-dimensional Tumor Spheroids Using Optical Coherence Tomography

三维肿瘤球体的纵向形态和生理监测

Tumor spheroids have been developed as a three-dimensional (3D) cell culture model in cancer research and anti-cancer drug discovery. However, currently, ...

Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy

通过高分辨率共聚焦显微镜对3D肿瘤球体入侵的影响表征

Drug discovery and development in cancer research is increasingly being based on drug screens in a 3D format. Novel inhibitors targeting the migratory and ...