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Grant Details

Grant Number: 5R00CA218603-04 Interpret this number
Primary Investigator: Brown, Justin
Organization: Lsu Pennington Biomedical Research Ctr
Project Title: Inflammation, Physical Activity, and Colon Cancer Recurrence and Survival
Fiscal Year: 2020


Abstract

PROJECT SUMMARY/ABSTRACT Systemic inflammation is associated with a higher risk of cancer recurrence and mortality among colon cancer patients. Systemic inflammation promotes the growth and progression of existing micro-metastases and the development of new distant metastases. Reducing systemic inflammation may decrease the risk of developing recurrent and metastatic disease among colon cancer patients. Epidemiologic data suggests that physical activity after diagnosis of colon cancer reduces the risk of recurrence and mortality by 50%. Physical activity possesses potent anti-inflammatory properties. However, the extent to which physical activity can normalize the host microenvironment by interrupting the crosstalk between inflammation and the growth and progression of existing micro-metastases and the development of new distant metastases is not known. We hypothesize that physical activity mediates the relationship between inflammation and cancer recurrence and mortality. Aim 1 will determine if physical activity mediates the relationship between plasma inflammatory markers and cancer recurrence and mortality among colon cancer patients. To complete this aim, we will utilize data from a recently-completed NCI-sponsored trial among 2,526 colon cancer patients. Aim 2 will determine preliminary effect size estimates for two distinct doses of exercise to reduce plasma inflammatory markers among colon cancer patients. To complete this aim, we will utilize data from a recently-completed NCI-sponsored phase II trial that randomized 39 colon cancer patients to low-dose (150 min/wk) or high-dose (300 min/wk) moderate- intensity aerobic exercise or a usual care control group for six-months. The results from Aims 1 and 2 will guide the design and implementation of Aim 3, which will determine the efficacy of exercise to reduce plasma inflammatory markers among colon cancer patients. To complete this aim, we will conduct an adequately- powered prospective randomized trial among colon cancer patients. This research and training plan will: 1) provide the advanced transdisciplinary training necessary to accelerate the translation of epidemiologic discoveries into efficacious individual and population level interventions; 2) position the applicant to emerge as an international leader in the field of energy balance and cancer outcomes research, and; 3) validate a translational platform on which to examine other biologic pathways to be funded through future research project grant programs (R01s). Understanding how physical activity may alter inflammation to favorably influence disease outcomes among colon cancer patients offers unique insight into colon cancer biology and provides new paradigms in cancer therapy by optimizing treatment strategies and identifying additional therapeutic targets. This research aligns with an NCI key priority area to elucidate the molecular basis through which exercise may influence cancer outcomes, towards the goal of optimizing exercise prescription to maximize patient outcomes.



Publications

Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.
Authors: Brown J.C. , Rosenthal M.H. , Ma C. , Zhang S. , Nimeiri H.S. , McCleary N.J. , Abrams T.A. , Yurgelun M.B. , Cleary J.M. , Rubinson D.A. , et al. .
Source: Cancers, 2020-11-20; 12(11), .
EPub date: 2020-11-20.
PMID: 33233566
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Obesity and Cancer: It's Causal and…Reversible?
Authors: Brown J.C. , McTiernan A. .
Source: Obesity (Silver Spring, Md.), 2020 Sep; 28(9), p. 1575.
PMID: 32841526
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Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial.
Authors: Brown J.C. , Zhang S. , Ligibel J.A. , Irwin M.L. , Jones L.W. , Campbell N. , Pollak M.N. , Sorrentino A. , Cartmel B. , Harrigan M. , et al. .
Source: Cancer prevention research (Philadelphia, Pa.), 2020-08-28; , .
EPub date: 2020-08-28.
PMID: 32859615
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An exercise oncology clinical pathway: Screening and referral for personalized interventions.
Authors: Stout N.L. , Brown J.C. , Schwartz A.L. , Marshall T.F. , Campbell A.M. , Nekhlyudov L. , Zucker D.S. , Basen-Engquist K.M. , Campbell G. , Meyerhardt J. , et al. .
Source: Cancer, 2020-06-15; 126(12), p. 2750-2758.
EPub date: 2020-03-25.
PMID: 32212338
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Physical Activity Reduces the Risk of Recurrence and Mortality in Cancer Patients.
Authors: Brown J.C. , Gilmore L.A. .
Source: Exercise and sport sciences reviews, 2020 04; 48(2), p. 67-73.
PMID: 31913187
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The Association of Abdominal Adiposity With Mortality in Patients With Stage I-III Colorectal Cancer.
Authors: Brown J.C. , Caan B.J. , Prado C.M. , Cespedes Feliciano E.M. , Xiao J. , Kroenke C.H. , Meyerhardt J.A. .
Source: Journal of the National Cancer Institute, 2020-04-01; 112(4), p. 377-383.
PMID: 31355882
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The Value of Anthropometric Measures in Nutrition and Metabolism: Comment on Anthropometrically Predicted Visceral Adipose Tissue and Blood-Based Biomarkers: A Cross-Sectional Analysis.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: Nutrition and metabolic insights, 2019; 12, p. 1178638819831712.
EPub date: 2019-02-27.
PMID: 30833814
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The evolution of body composition in oncology-epidemiology, clinical trials, and the future of patient care: facts and numbers.
Authors: Brown J.C. , Cespedes Feliciano E.M. , Caan B.J. .
Source: Journal of cachexia, sarcopenia and muscle, 2018 Dec; 9(7), p. 1200-1208.
EPub date: 2019-01-13.
PMID: 30637983
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Lifestyle Interventions for Breast Cancer Prevention.
Authors: Brown J.C. , Ligibel J.A. .
Source: Current breast cancer reports, 2018 Sep; 10(3), p. 202-208.
EPub date: 2018-07-03.
PMID: 30713591
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Self-reported major mobility disability and mortality among cancer survivors.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: Journal of geriatric oncology, 2018 09; 9(5), p. 459-463.
EPub date: 2018-03-14.
PMID: 29550343
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The deterioration of muscle mass and radiodensity is prognostic of poor survival in stage I-III colorectal cancer: a population-based cohort study (C-SCANS).
Authors: Brown J.C. , Caan B.J. , Meyerhardt J.A. , Weltzien E. , Xiao J. , Cespedes Feliciano E.M. , Kroenke C.H. , Castillo A. , Kwan M.L. , Prado C.M. .
Source: Journal of cachexia, sarcopenia and muscle, 2018 08; 9(4), p. 664-672.
EPub date: 2018-05-15.
PMID: 29766660
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Applying pre-participation exercise screening to breast cancer survivors: a cross-sectional study.
Authors: Igwebuike L.T. , Zhang X. , Brown J.C. , Schmitz K.H. .
Source: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018 Jun; 26(6), p. 1825-1831.
EPub date: 2017-12-19.
PMID: 29260391
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A randomized dose-response trial of aerobic exercise and health-related quality of life in colon cancer survivors.
Authors: Brown J.C. , Damjanov N. , Courneya K.S. , Troxel A.B. , Zemel B.S. , Rickels M.R. , Ky B. , Rhim A.D. , Rustgi A.K. , Schmitz K.H. .
Source: Psycho-oncology, 2018 04; 27(4), p. 1221-1228.
EPub date: 2018-02-20.
PMID: 29388275
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Randomized trial of a clinic-based weight loss intervention in cancer survivors.
Authors: Brown J.C. , Yung R.L. , Gobbie-Hurder A. , Shockro L. , O'Connor K. , Campbell N. , Kasper J. , Mayer E.L. , Tolaney S.M. , Partridge A.H. , et al. .
Source: Journal of cancer survivorship : research and practice, 2018 04; 12(2), p. 186-195.
EPub date: 2017-11-03.
PMID: 29101711
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Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer.
Authors: Brown J.C. , Rhim A.D. , Manning S.L. , Brennan L. , Mansour A.I. , Rustgi A.K. , Damjanov N. , Troxel A.B. , Rickels M.R. , Ky B. , et al. .
Source: PloS one, 2018; 13(10), p. e0204875.
EPub date: 2018-10-17.
PMID: 30332430
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Dose-response effects of exercise on insulin among colon cancer survivors.
Authors: Brown J.C. , Rickels M.R. , Troxel A.B. , Zemel B.S. , Damjanov N. , Ky B. , Rhim A.D. , Rustgi A.K. , Courneya K.S. , Schmitz K.H. .
Source: Endocrine-related cancer, 2018 01; 25(1), p. 11-19.
EPub date: 2017-10-10.
PMID: 29018055
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The Role of Physical Activity in Oncology Care.
Authors: Brown J.C. , Ligibel J.A. .
Source: Journal of the National Cancer Institute. Monographs, 2017-11-01; 2017(52), .
PMID: 29140498
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Putting Exercise Into Oncology Practice: State-of-the-Science, Innovation, and Future Directions.
Authors: Brown J.C. , Ligibel J.A. .
Source: Cancer journal (Sudbury, Mass.), 2019 Sep/Oct; 25(5), p. 316-319.
PMID: 31567458
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