Analysis of Radiation-Induced Cell Death in Head and Neck Squamous Cell Carcinoma and Rat Liver Maintained in Microfluidic Devices
Analysis of Radiation-Induced Cell Death in Head and Neck Squamous Cell Carcinoma and Rat Liver Maintained in Microfluidic Devices
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DOI：
10.1177/0194599813507427
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发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Greenman, John
中科院分区：
文献类型：
--
作者：
Carr, Simon D.;Green, Victoria L.;Greenman, John
目的本研究的目的是探讨如何保持在一个定制的微流控装置内的伪体内环境头颈部鳞状细胞癌（HNSCC）组织活检放射treatment.Study设计可行性研究设置三级转诊center.Subjects和方法35例HNSCC患者被招募，肝组织从5只Wistar大鼠。使用微流体装置将组织活检样品维持在存活状态。以大鼠肝脏为实验材料，对方法学进行了优化。HNSCC取自T1-T3喉或口咽SCC患者;还获得了N1-N2转移性颈部淋巴结。照射包括2戈伊至40戈伊的单次剂量和5 × 2戈伊的分次疗程。细胞死亡进行了评估，在组织流出液中使用的可溶性标记物乳酸脱氢酶（LDH）和细胞色素c和在组织中通过免疫组化检测裂解细胞角蛋白18（M30抗体）。结果一个显着的激增，LDH释放后，大鼠肝脏表现出单次剂量为20戈伊，在HNSCC，它被认为是40戈伊后与对照组相比。5戈伊和10戈伊照射后细胞色素c释放量无显著差异。M30表现出剂量依赖性增加的细胞凋亡指数为一个给定的增加单剂量放疗。结论与可溶性标记物相比，M30标记物在检测低剂量辐射诱导的细胞死亡方面具有上级的应用价值。这种微流控技术可用于评估HNSCC中辐射诱导的细胞死亡，因此有可能用于预测辐射反应。
Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment.Study Design Feasibility study.Setting Tertiary referral center.Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5x2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody).Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1x2 Gy and 5x2 Gy.Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response.