Introduction: Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered lifelong survival, cancer incidence, and morbidity. Methods: Male CBA mice were randomly divided into control diet/sedentary group (CTRL/SED), high-fat diet (45% fat)/sedentary group (HFD/SED), control diet/exercise group (2-3 d•wk −1 ; CTRL/EX), or high-fat diet/exercise group (HFD/EX) groups then exposed to whole-body radiation (3 Gy). End point monitoring and pathology determined mortality and cancer incidence, respectively. Health span index, a measure of morbidity, was determined by a composite measure of 10 anthropometric, metabolic, performance, and behavioral measures. Results: Overall survival was higher in HFD/SED compared with CTRL/SED (P < 0.05). The risk of cancer-related mortality by 18 months postradiation was 1.99 and 1.63 in HFD/SED compared with CTRL/EX (RR = 1.99, 95% confidence interval = 1.20-3.31, P = 0.0081) and CTRL/SED (RR = 1.63, 95% confidence interval = 1.06-2.49, P = 0.0250), respectively. The number of mice at end point with cancer was higher in HFD/SED compared with CTRL/EX and CTRL/SED (P < 0.05). Health span index was highest in CTRL/EX (score = +2.5), followed by HFD/EX (score = +1), and HFD/SED (score = −1) relative to CTRL/SED. Conclusion: This work provides the basis for future preclinical studies investigating the dose-response relationship between exercise training and late effects of radiation therapy as well as the mechanisms responsible for these effects.
The IgNITE Medical Case Competition is an annual research case competition organized by students at the University of Ottawa. Our mission is to provide high school and university students the opportunity to gain valuable research experience while networking with industry professionals. Each year students, in teams of 1-4, are paired with an experienced mentor to develop and present a novel research proposal within the specified theme of the competition. During the competition, students are taught the fundamental principles underlying three lab techniques which they can then use in their proposal or their future research career. This year’s theme was Regenerative Medicine and competitors learned about Immunofluorescence, Western Blot, and CRISPR-Cas9. In 2020-2021 the IgNITE community grew internationally with 570 high school and university students across the world participating in the competition. In this booklet we present the Top 40 teams and invite you to visit our website (www.ignitecompetition.org) to watch their pitch proposal videos. We hope you enjoy reading through some of this year’s top proposals and invite you to join our growing community.
There are nearly 16 million cancer survivors living in the United States today, with two‐thirds of them having received radiation therapy as part of their treatment. Furthermore, there is a concurrent increase in obesity and physical inactivity among this population. Combined with the effects of ionizing radiation (IR), these host factors are increasing the risk of secondary, treatment‐induced cancers and may contribute to poor healthspan outcomes in cancer survivors. As such, a critical need exists to develop a better understanding of how these host factors interact with radiation exposure, such that we can provide cancer survivors with better lifestyle recommendations to enhance their overall quality of life and decrease their secondary cancer risk. Male CBA mice were randomly divided into a control diet group (CTRL) or a 45% high fat diet group (HFD) to induce obesity. At nine weeks of age, half of the mice in each dietary group began a treadmill exercise training intervention (EX), or remained sedentary (SED), and were then all exposed to ionizing radiation (3 Gy) at 13 weeks of age. Healthspan was measured in each group at 17 months of age by assessing: endurance performance, metabolic and locomotor activity, depression‐like behaviour, forelimb grip strength and plasma clinical chemistry. Endurance performance was significantly greater in CTRL/EX compared to both HFD groups 5 days pre‐IR and compared to both SED groups 5 months post‐IR (both p<0.05). Metabolic analysis revealed a significant increase in the respiratory exchange ratio in CTRL compared to HFD mice (p<0.05), but there were no significant differences in O2 consumption, CO2, or heat production (p>0.05). There was also a trend for an increase in locomotor activity in the CTRL/EX compared to CTRL/SED group during their light and dark cycle (p = 0.06 and p = 0.108, respectively). Further, there was a significant decrease in depression‐like behaviour among HFD compared to CTRL mice, and EX compared to SED mice (p<0.05), as well as a significant decrease in forelimb grip strength normalized to body weight among HFD compared to CTRL mice (p<0.05). Additionally, there was a significant increase in total cholesterol levels among HFD compared to CTRL mice (p<0.05). Interestingly, the CTRL/EX and HFD/EX groups had a 20% decrease in cancer incidence compared to the HFD/SED group, and EX mice had a 17.5% decrease in cancer incidence compared to SED mice, independent of diet (both p>0.05). Our current findings suggest that long‐term exercise and dietary interventions should be implemented in cancer survivors exposed to radiation therapy in order to improve healthspan and potentially protect against secondary cancer incidence. Support or Funding Information The American Institute of Cancer Research (AICR), The Natural Sciences and Engineering Research Council of Canada (NSERC), and The Canadian Institutes of Health Research (CIHR)
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