Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy

  • Authors:
    • Ramsah Cheah
    • Rishi Srivastava
    • Nicholas D. Stafford
    • Andrew W. Beavis
    • Victoria Green
    • John Greenman
  • View Affiliations

  • Published online on: September 5, 2017     https://doi.org/10.3892/ijo.2017.4118
  • Pages:1227-1238
Metrics: PDF 0 views | HTML 0 views
0

Abstract

Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers. HNSCC biopsies from five newly-presenting patients [2 lymph node (LN); 3 primary tumour (PT)] were divided into parallel microfluidic devices and replicates of each tumour were subjected to single-dose irradiation (0, 5, 10, 15 and 20 Gy). Lactate dehydrogenase (LDH) release was measured and tissue sections were stained for cytokeratin (CK), cleaved-CK18 (cCK18), phosphorylated-H2AX (γH2AX) and Ki‑67 by immunohistochemistry. In addition, fragmented DNA was detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Compared with non‑irradiated controls, higher irradiation doses resulted in elevated CK18-labelling index in two lymph nodes [15 Gy; 34.8% on LN1 and 31.7% on LN2 (p=0.006)] and a single laryngeal primary tumour (20 Gy; 31.5%; p=0.014). Significantly higher levels of DNA fragmentation were also detected in both lymph node samples and one primary tumour but at varying doses of irradiation, i.e., LN1 (20 Gy; 27.6%; p=0.047), LN2 (15 Gy; 15.3%; p=0.038) and PT3 (10 Gy; 35.2%; p=0.01). The γH2AX expression was raised but not significantly in the majority of samples. The percentage of Ki‑67 positive nuclei reduced dose-dependently following irradiation. In contrast no significant difference in LDH release was observed between irradiated groups and controls. There is clear inter- and intra-patient variability in response to irradiation when measuring a variety of parameters, which offers the potential for the approach to provide clinically valuable information.

Related Articles

Journal Cover

October 2017
Volume 51 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Cheah, R., Srivastava, R., Stafford, N.D., Beavis, A.W., Green, V., & Greenman, J. (2017). Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy. International Journal of Oncology, 51, 1227-1238. https://doi.org/10.3892/ijo.2017.4118
MLA
Cheah, R., Srivastava, R., Stafford, N. D., Beavis, A. W., Green, V., Greenman, J."Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy". International Journal of Oncology 51.4 (2017): 1227-1238.
Chicago
Cheah, R., Srivastava, R., Stafford, N. D., Beavis, A. W., Green, V., Greenman, J."Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy". International Journal of Oncology 51, no. 4 (2017): 1227-1238. https://doi.org/10.3892/ijo.2017.4118