PMID- 32330594 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20210918 IS - 1090-2139 (Electronic) IS - 0889-1591 (Print) IS - 0889-1591 (Linking) VI - 88 DP - 2020 Aug TI - Pilot study of combined aerobic and resistance exercise on fatigue for patients with head and neck cancer: Inflammatory and epigenetic changes. PG - 184-192 LID - S0889-1591(19)31283-8 [pii] LID - 10.1016/j.bbi.2020.04.044 [doi] AB - This pilot study examined whether a combined aerobic resistance exercise program reduced fatigue and the potential inflammatory and epigenetic mechanisms in patients with head and neck cancer (HNC) receiving intensity-modulated radiotherapy. The exercise group (N = 12) received a 3-month supervised aerobic resistance exercise intervention that was initiated before a 6-week radiotherapy regimen; the control group (N = 14) received standard care. Fatigue was measured using Multidimensional Fatigue Inventory-20; physical function measures included a 6-minute walk distance (6MWD), chair stands, bicep curls, and hand grip strength. Inflammatory markers and DNA methylation data were acquired using standardized protocol. Patients were mostly white (93%) and male (81%) with a mean age of 57 years. At the end of the intervention, the exercise group had a marginal decrease in fatigue compared with the control (-5.0 vs. 4.9; P = 0.10). The exercise group had a significantly greater improvement in 6MWD (29.8 vs. -55.5 m; P = 0.04), and a marginally smaller decline in hand grip (-0.3 vs. -5.8 lbs; P = 0.05) at the end of the intervention than the control. No significant difference in inflammatory markers was observed between groups. Lower plasma interleukin (IL) 6, IL1 receptor antagonist, tumor necrosis factor alpha (TNFalpha), soluble TNF receptor II and C-reactive protein were significantly associated with increased 6MWD, chair stand, and bicep curl at the end of the intervention (p < 0.05). Among the 1152 differentially methylated sites (DMS) after intervention (p < 0.001), 163 DMS were located in gene promoter regions. Enrichment analysis suggested that the top 10 upstream regulators were associated with tumor (HNF4A, RPP38, HOXA9, SAHM1, CDK7, NDN, RPS15) and inflammation (IRF7, CRKL, ONECUT1). The top 5 diseases or functions annotations of the 62 hypermethylated DMS indicated anti-tumor and anti-inflammatory effects that might be linked to exercise. These findings suggest that exercise may improve physical performance and reduce fatigue, which could be further linked to decreased inflammation, during active radiotherapy for HNC patients. Larger studies are warranted. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Xiao, Canhua AU - Xiao C AD - School of Nursing, Yale University, 400 West Campus Drive, Orange 06477, United States. Electronic address: canhua.xiao@yale.edu. FAU - Beitler, Jonathan J AU - Beitler JJ AD - Department of Radiation, School of Medicine, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States. FAU - Higgins, Kristin A AU - Higgins KA AD - Department of Radiation, School of Medicine, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States. FAU - Chico, Cynthia E AU - Chico CE AD - Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA 30322, United States. FAU - Withycombe, Janice S AU - Withycombe JS AD - School of Nursing, Clemson University, 508 Edward's, Clemson, SC 29634, United States. FAU - Zhu, Ying AU - Zhu Y AD - State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200433, China. FAU - Zhao, Hongyu AU - Zhao H AD - Department of Epidemiology and Public Health, School of Medicine, Yale University, 300 George Street, New Haven, CT 06510, United States. FAU - Lin, I-Hsin AU - Lin IH AD - Yale Center for Analytical Sciences, School of Public Health, Yale University, 300 George Street, New Haven, CT 06510, United States. FAU - Li, Fangyong AU - Li F AD - School of Public Health, Yale University, 60 College St, New Haven, CT 06510, United States. FAU - Jeon, Sangchoon AU - Jeon S AD - School of Nursing, Yale University, 400 West Campus Drive, Orange 06477, United States. FAU - Irwin, Melinda AU - Irwin M AD - School of Public Health, Yale University, 60 College St, New Haven, CT 06510, United States. FAU - Bruner, Deborah W AU - Bruner DW AD - School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States. FAU - Miller, Andrew H AU - Miller AH AD - Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA 30322, United States. FAU - Gary, Rebecca AU - Gary R AD - School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States. LA - eng GR - P30 CA138292/CA/NCI NIH HHS/United States GR - R01 NR015783/NR/NINR NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200421 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 SB - IM MH - Epigenesis, Genetic MH - Fatigue MH - Hand Strength MH - *Head and Neck Neoplasms MH - Humans MH - Male MH - Middle Aged MH - Pilot Projects MH - Quality of Life MH - *Resistance Training PMC - PMC7415514 MID - NIHMS1587804 OTO - NOTNLM OT - DNA methylation OT - Exercise OT - Fatigue OT - Inflammation COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/04/25 06:00 MHDA- 2021/04/28 06:00 PMCR- 2021/08/01 CRDT- 2020/04/25 06:00 PHST- 2019/10/17 00:00 [received] PHST- 2020/04/17 00:00 [revised] PHST- 2020/04/17 00:00 [accepted] PHST- 2020/04/25 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/04/25 06:00 [entrez] PHST- 2021/08/01 00:00 [pmc-release] AID - S0889-1591(19)31283-8 [pii] AID - 10.1016/j.bbi.2020.04.044 [doi] PST - ppublish SO - Brain Behav Immun. 2020 Aug;88:184-192. doi: 10.1016/j.bbi.2020.04.044. Epub 2020 Apr 21.