Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer
| dc.contributor.author | Van Nest, Samantha J. | |
| dc.contributor.author | Nicholson, Leah M. | |
| dc.contributor.author | Pavey, Nils | |
| dc.contributor.author | Hindi, Mathew N. | |
| dc.contributor.author | Brolo, Alexandre G. | |
| dc.contributor.author | Jirasek, Andrew | |
| dc.contributor.author | Lum, Julian J. | |
| dc.date.accessioned | 2020-11-02T20:57:04Z | |
| dc.date.available | 2020-11-02T20:57:04Z | |
| dc.date.copyright | 2019 | en_US |
| dc.date.issued | 2019 | |
| dc.description.abstract | Background Radiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear. Methods We used an established Raman spectroscopic (RS) technique in combination with immunofluorescence staining to measure radiation-induced metabolic responses in human non-small cell lung cancer (NSCLC) tumour xenografts. Tumours were established in NOD.CB17-Prkdcscid/J mice, and were exposed to radiation doses of 15 Gy or left untreated. Tumours were harvested at 2 h, 1, 3 and 10 days post irradiation. Results We report that xenografted NSCLC tumours demonstrate rapid and stable metabolic changes, following exposure to 15 Gy radiation doses, which can be measured by RS and are dictated by the extent of local tissue oxygenation. In particular, fluctuations in tissue glycogen content were observed as early as 2 h and as late as 10 days post irradiation. Metabolically, this signature was correlated to the extent of tumour regression. Immunofluorescence staining for γ–H2AX, pimonidazole and carbonic anhydrase IX (CAIX) correlated with RS-identified metabolic changes in hypoxia and reoxygenation following radiation exposure. Conclusion Our results indicate that RS can identify sequential changes in hypoxia and tumour reoxygenation in NSCLC, that play crucial roles in radiosensitivity. | en_US |
| dc.description.reviewstatus | Reviewed | en_US |
| dc.description.scholarlevel | Faculty | en_US |
| dc.description.sponsorship | This work was supported by grant funding from CIHR (258926, AGB, AJ, JJL), CFI (32859, AGB, AJ), The BC Cancer Foundation (JJL) and NSERC CGS-D (SJV). The role of the funders was to provide financial support in equipment and operations costs. | en_US |
| dc.identifier.citation | Van Nest, S. J., Nicholson, L. M., Pavey, N., Hindi, M. N., Brolo, A. G., Jirasek, A., … Lum, J. L. (2019) Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer. BMC Cancer, 2019. https://doi.org/10.1186/s12885-019-5686-1 | en_US |
| dc.identifier.uri | https://doi.org/10.1186/s12885-019-5686-1 | |
| dc.identifier.uri | http://hdl.handle.net/1828/12288 | |
| dc.language.iso | en | en_US |
| dc.publisher | BMC Cancer | en_US |
| dc.subject | Raman spectroscopy | |
| dc.subject | Non-small cell lung cancer | |
| dc.subject | Hypoxia | |
| dc.subject | Reoxygenation | |
| dc.subject | Ionizing radiation | |
| dc.subject | Immunofluorescence | |
| dc.subject.department | Department of Physics and Astronomy | |
| dc.subject.department | Department of Chemistry | |
| dc.subject.department | Department of Biochemistry and Microbiology | |
| dc.title | Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer | en_US |
| dc.type | Article | en_US |