Analysis of radiation effects in two irradiated tumor spheroid models.
Analysis of radiation effects in two irradiated tumor spheroid models.
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分析两个辐照的肿瘤球体模型中的辐射效应。
DOI：
10.3892/ol.2017.7716
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发表时间：
2018-03
期刊：
影响因子：
2.9
通讯作者：
Nestor MV
中科院分区：
文献类型：
--
作者：
Al-Ramadan A;Mortensen AC;Carlsson J;Nestor MV
多细胞球体已被证明适合作为非血管化微转移的三维体内样模型。与基于单层的模型不同，球状体反映了肿瘤结节内的细胞环境和病理生理梯度。然而，人们对源自人类的球体在分子水平上的辐射效应的了解有限。本研究介绍了选定的细胞生物学过程，可以很容易地用常规病理学实验室可用的方法进行分析。本研究使用伽马辐照胰腺神经内分泌B0N 1和结肠腺癌HCT 116球体作为模型系统，评估这些模型中的放射生物学反应。随着时间的推移，跟踪照射后的球体生长，随后用免疫组织化学（IHC）染色评估分子反应，用于描述性分析和球体薄切片中细胞凋亡、G2期和衰老的半自动分级。生长研究表明，与HCT 116球状体相比，BON1球状体生长较慢，对辐射不太敏感。G2期的IHC染色主要在球状体的外部活P细胞层中观察到，与未照射的球状体相比，6戈伊照射的HCT 116球状体显示出染色强度非常明显的增加。细胞凋亡染色结果显示细胞凋亡随着辐射剂量的增加而增加。在球状体中没有观察到衰老和辐射暴露之间的明确关联。目前的结果表明，使用多细胞球体的人源性结合免疫组化分析，以解开在分子水平上的放射生物学反应的可行性。目前的研究结果激发了进一步的研究，包括其他相关的IHC检测的分子过程中的时间和辐射剂量依赖性的设置。
Multicellular spheroids have proven suitable as three-dimensional in vivo-like models of non-vascularized micrometastases. Unlike monolayer-based models, spheroids mirror the cellular milieu and the pathophysiological gradients inside tumor nodules. However, there is limited knowledge of the radiation effects at the molecular level in spheroids of human origin. The present study is a presentation of selected cell biological processes that may easily be analyzed with methods available at routine pathology laboratories. Using gamma irradiated pancreatic neuroendocrine BON1 and colonic adenocarcinoma HCT116 spheroids as model systems, the present study assessed the radiobiological response in these models. Spheroid growth after irradiation was followed over time and molecular responses were subsequently assessed with immunohistochemistry (IHC) staining for descriptive analyses and semi-automatic grading of apoptosis, G2-phase and senescence in thin sections of the spheroids. Growth studies demonstrated the BON1 spheroids were slower growing and less sensitive to radiation compared with the HCT116 spheroids. IHC staining for G2-phase was primarily observed in the outer viable P-cell layers of the spheroids, with the 6 Gy irradiated HCT116 spheroids demonstrating a very clear increase in staining intensity compared with unirradiated spheroids. Apoptosis staining results indicated increased apoptosis with increasing radiation doses. No clear association between senescence and radiation exposure in the spheroids were observed. The present results demonstrate the feasibility of the use of multicellular spheroids of human origin in combination with IHC analyses to unravel radiobiological responses at a molecular level. The present findings inspire further investigations, including other relevant IHC-detectable molecular processes in time- and radiation dose-dependent settings.
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影响因子：
8.8
作者：
通讯作者：
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影响因子：
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作者：
Ivascu, Andrea;Kubbies, Manfred
通讯作者：
Kubbies, Manfred
影响因子：
4.3
作者：
Kim, Jung Ho;Hyun, Chang Lim;Han, Sang Hoon
通讯作者：
Han, Sang Hoon
DOI：
10.1016/0360-3016(95)02065-9
发表时间：
1996-01-15
影响因子：
7
作者：
Groebe, K;MuellerKlieser, W
通讯作者：
MuellerKlieser, W
影响因子：
5.2
作者：
Qvarnstrom, O. F.;Simonsson, M.;Carlsson, J.
通讯作者：
Carlsson, J.