title: A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs.
abstract: 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.
authors: Centre for Biomedical Research, Postgraduate Medical Institute, University of Hull, Cottingham Road, Kingston upon Hull, HU6 7RX, UK.
authors: Samantha M
authors: SM
authors: Hattersley
authors: Deborah C
authors: DC
authors: Sylvester
authors: Charlotte E
authors: CE
authors: Dyer
authors: Nicholas D
authors: ND
authors: Stafford
authors: Stephen J
authors: SJ
authors: Haswell
authors: John
authors: J
authors: Greenman
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D009363:Neoplasm Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; D045304:Cytochromes c; D006836:Hydro-Lyases; C045581:lactate dehydratase; D002945:Cisplatin; D005472:Fluorouracil