Ontology highlight
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 ?-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.
SUBMITTER: Van Nest SJ
PROVIDER: S-EPMC6528330 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Van Nest Samantha J SJ Nicholson Leah M LM Pavey Nils N Hindi Mathew N MN Brolo Alexandre G AG Jirasek Andrew A Lum Julian J JJ
BMC cancer 20190520 1
<h4>Background</h4>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.<h4>Methods</h ...[more]