Centre for Biomedical Research, Postgraduate Medical Institute, University of Hull, Cottingham Road, Kingston upon Hull, HU6 7RX, UK.
Ann Biomed Eng. 2012 Jun;40(6):1277-88. doi: 10.1007/s10439-011-0428-9. Epub 2011 Oct 15.
Tumors are heterogeneous masses of cells characterized pathologically by their size and spread. Their chaotic biology makes treatment of malignancies hard to generalize. We present a robust and reproducible glass microfluidic system, for the maintenance and "interrogation" of head and neck squamous cell carcinoma (HNSCC) tumor biopsies, which enables continuous media perfusion and waste removal, recreating in vivo laminar flow and diffusion-driven conditions. Primary HNSCC or metastatic lymph samples were subsequently treated with 5-fluorouracil and cisplatin, alone and in combination, and were monitored for viability and apoptotic biomarker release 'off-chip' over 7 days. The concentration of lactate dehydrogenase was initially high but rapidly dropped to minimally detectable levels in all tumor samples; conversely, effluent concentration of WST-1 (cell proliferation) increased over 7 days: both factors demonstrating cell viability. Addition of cell lysis reagent resulted in increased cell death and reduction in cell proliferation. An apoptotic biomarker, cytochrome c, was analyzed and all the treated samples showed higher levels than the control, with the combination therapy showing the greatest effect. Hematoxylin- and Eosin-stained sections from the biopsy, before and after maintenance, demonstrated the preservation of tissue architecture. This device offers a novel method of studying the tumor environment, and offers a pre-clinical model for creating personalized treatment regimens.
肿瘤是由细胞组成的异质性肿块，其大小和扩散程度在病理学上具有特征性。它们混乱的生物学特性使得恶性肿瘤的治疗难以概括。我们提出了一种稳健且可重复的玻璃微流控系统，用于维持和“询问”头颈部鳞状细胞癌（HNSCC）肿瘤活检，该系统能够实现连续的介质灌注和废物去除，重现体内层流和扩散驱动的条件。随后，将原发性 HNSCC 或转移性淋巴结样本单独或联合用 5-氟尿嘧啶和顺铂进行处理，并在 7 天内监测其在“片外”的活力和凋亡生物标志物释放情况。乳酸脱氢酶的浓度最初很高，但在所有肿瘤样本中迅速降至最低检测水平；相反，WST-1（细胞增殖）的流出浓度在 7 天内增加：这两个因素都表明细胞活力。加入细胞裂解试剂会导致细胞死亡增加和细胞增殖减少。分析了凋亡生物标志物细胞色素 c，所有处理样本的水平均高于对照，联合治疗的效果最大。维持前后，活检的苏木精和伊红染色切片显示组织结构得到了保存。该装置提供了一种研究肿瘤环境的新方法，并为创建个性化治疗方案提供了临床前模型。
