Abstract
461 - Metabolic Plasticity Regulates Head and Neck Squamous Cell Cancer Growth-State Specific Oxidative Stress Response
Free radical biology & medicine, Vol.100, pp.S191-S192
11/2016
DOI: 10.1016/j.freeradbiomed.2016.10.524
Abstract
Surgical resection followed by post-operative radiation is used as a standard treatment approach for locally advanced head and neck squamous cell cancer (HNSCC) patients. Unfortunately, even with aggressive approaches roughly 40% of patients with locoregionally advanced disease will ultimately succumb. 18F- Fluorothymidine Positron Emission Tomography (FLT PET) is a non-invasive imaging method that can be used in vivo to assess tumor proliferative status. Results showed that FLT PET successfully images HNSCC subjects with high lesion-to-background contrast. Surprisingly, our results also showed that HNSCC subjects with low FLT uptake (indicative of low proliferative index; LPI) in the primary tumor at base line have significantly poorer outcome compared to subjects with high tumor FLT uptake (indicative of high proliferative index; HPI). This intriguing clinical observation suggests that HNSCC growth-state significantly impacts therapy outcome. Consistent with this hypothesis, results from in vitro HNSCC cell culture studies showed that LPI-HNSCC cultures (<10% S-phase cells) are radioresistant compared to their corresponding HPI-HNSCC cultures (>20% S-phase cells). Radioresistance of LPI-HNSCC cultures is associated with a higher basal manganese superoxide dismutase activity, increases in radiation induced forkhead box M1 expression, suppression of late accumulation of reactive oxygen species (ROS), and absence of a radiation induced shift in cellular metabolism towards mitochondrial respiration. Interestingly, treatment with palmitate (substrate for the TCA cycle) increased oxygen consumption rate and ROS levels resulting in radiation sensitization of LPI-HNSCC cultures. These results support the hypothesis that metabolic plasticity regulates HNSCC growth-state specific radiation sensitivity.
Details
- Title: Subtitle
- 461 - Metabolic Plasticity Regulates Head and Neck Squamous Cell Cancer Growth-State Specific Oxidative Stress Response
- Creators
- Amanda L KalenEhab H SarsouWafa A AshaJyungmean SonYusuf MendaJohn M BuattiPrabhat C Goswami
- Resource Type
- Abstract
- Publication Details
- Free radical biology & medicine, Vol.100, pp.S191-S192
- DOI
- 10.1016/j.freeradbiomed.2016.10.524
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/2016
- Academic Unit
- Radiology; Radiation Oncology; Neurosurgery; Otolaryngology
- Record Identifier
- 9984305133902771
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