Abstract
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. Feasibility study. Tertiary referral center. 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 5×2 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). 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 1×2 Gy and 5×2 Gy. 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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) accounted for 2.8/100,000 of all cancers in the UK in 2011 and represents the seventh most common cancer in Europe 1
A significant surge in lactate dehydrogenase (LDH) release was demonstrated in the rat liver after a single dose of 20Gy; in HNSCC it was seen after 40Gy compared to the control
The soluble markers used in this study to determine the effects of radiation treatment on HNSCC tissue maintained in a microfluidic device were lactate dehydrogenase (LDH), an intracellular enzyme, and cytochrome c, which is stored in the mitochondria and is responsible for the stimulation of caspases as part of the apoptotic cascade; both of these factors are released from membrane compromised cells
Summary
Head and neck squamous cell carcinoma (HNSCC) accounted for 2.8/100,000 of all cancers in the UK in 2011 and represents the seventh most common cancer in Europe 1. Microfluidic devices provide a simple, reproducible and highly versatile system for maintaining tissue biopsies, allowing the tissue to remain viable and functional by preserving the three-dimensional architecture and its in vivo microenvironment [8,9,10]. This microenvironment enables cell-cell and cell-matrix interactions to be maintained 11, which govern the behaviour of tumour cells. The aim was to use a simple microfluidic device to detect the radiation-induced cell death of HNSCC biopsy samples, with the ultimate goal being the development of a tool capable of predicting the response of a patient’s HNSCC to radiotherapy on an individual basis prior to the commencement of treatment
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