Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen ...deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression.
We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety.
Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).
Doxorubicin (DOX) is a chemotherapeutic drug used to treat a wide range of cancers, and its use is limited by cardiotoxicity. Exercise preconditioning has been shown to protect against DOX‐induced ...cardiac dysfunction when hearts are maintained under resting conditions. However, it is unclear whether this exercise‐induced protective effect is maintained when the heart is challenged during an acute exercise bout. It was hypothesized that preconditioning protects the heart against DOX cardiotoxicity when it is challenged with the β1‐adrenergic receptor agonist dobutamine (DOB), which mimics acute exercise stress.
Fischer 344 rats were randomly assigned to sedentary (SED) or voluntary wheel running (WR) groups for 10 weeks. At week 11, rats were treated with either 15 mg/kg DOX or saline (SAL). Five days later, ex vivo cardiac function was assessed using an isolating working heart model at baseline, during the infusion of 7.5 μg/kg/min DOB, and during recovery.
DOB infusion significantly increased left ventricular developed pressure (LVDP), maximal (dP/dtmax) and minimal (dP/dtmin) rate of left ventricular pressure development, and heart rate in all groups (p<0.05). During the recovery phase (i.e., after DOB washout) LVDP was significantly lower than baseline in all groups except for SED+DOX (baseline vs. recovery: SED+SAL: 97±2 vs. 84±5 mmHg; WR+SAL: 116±7 vs. 90±7 mmHg; SED+DOX: 83±5 vs. 76±4 mmHg; WR+DOX: 109+2 vs. 100±4 mmHg, p<0.05). SED+DOX also showed a lower baseline and recovery LVDP than WR+DOX (83±5 vs. 109±2 mmHg baseline, 76±4 vs. 100±4 mmHg recovery, p<0.05). WR+DOX showed higher dP/dtmax and lower dP/dtmin when compared to SED+DOX during DOB infusion (7311±605 vs. 5167±508 mmHg/s and ‐4059±454 vs. ‐3158±416 mmHg/s, respectively). SED+DOX dP/dtmax was significantly lower during DOB infusion and during recovery when compared to all other groups (p<0.05). During DOB and recovery, +DOX groups showed lower HR values than +SAL groups (p<0.05).
These data demonstrate that exercise preconditioning preserved cardiac function after DOX exposure even when the heart is challenged, and it appeared to preserve the heart’s ability to recovery from this functional challenge. Cardioprotection seems to extend beyond rest into conditions which challenge cardiac function. These observations support the premise that exercise training can protect against cardiac dysfunction that may occur during acute exercise in cancer patients undergoing DOX treatment.
Breast cancer (BC) is one of the leading causes of cancer deaths among females. It is well known that the presence of a tumor decreases robust anticancer immunity via immunemodulation and enhanced ...immunosuppression through a process called cancer immunoediting. However, it has yet to be determined if exercise-based rehabilitation can elevate the peripheral anticancer immune profile and reduce myeloid-derived suppressor cell (MDSC) mediated immunosuppression. Purpose: To assess the effects of a 12-week prescribed, individualized, supervised exercise-based rehabilitation program on selected circulating immune cells in BC patients at the University of Northern Colorado Cancer Rehabilitation Institute. Methods: 16 female BC patients currently undergoing treatment were divided into a control group (CON, n=7), engaging in normal activities of daily living, and an exercise group (EX, n=9) that participated in 12-weeks of personalized combined aerobic and resistance training three times a week. Venous blood was collected before and after the intervention period and circulating immune cells will be analyzed for frequency and function using flow cytometry. Results: Early (E-) MDSC levels were significantly lower after the exercise intervention compared to the CON group (CON: 18.2±14.5% vs. EX: 5.3±3.6%, p<0.05). Monocytic (M-) MDSC showed a non-significant change of +48% in the CON group at POST (CON: PRE: 4.5±5.1% vs. POST: 6.8±4.5%), while POST M-MDSC levels displayed a non-significant change of -40% in the EX group (EX: PRE 4.9±2.6% vs. POST: 2.9±1.7%). An alternative MDSC phenotype analysis revealed that exercise significantly decreased M-MDSC from PRE to POST in the EX group (0.15±0.13% vs. 0.05± 0.03%, p<0.05), but not in the CON group (0.10±0.11% vs. 0.06±0.05%). There was no effect of exercise on MDSC suppressive activity or type I interferon receptor (IFNAR1) protein expression. The EX group displayed significantly higher levels of circulating Natural Killer (NK) cell frequencies than CON at the POST timepoint (3.5± 6.5 vs. 1.5±3.0 % of CD3- cells, p<0.05), where NK cell level changes were -75% for CON vs. +2% for EX from PRE to POST. There was a significant reduction in CD8+ cytotoxic T lymphocyte (CTLs) and CD4+ T helper (Th) cell frequencies in the EX group when comparing PRE to POST (CTLs: 23.6±10.8 vs. 16.1±10.1 % of CD3+ cells; Th: 41.3±24.3 vs. 27.5±21.1 % of CD3+ cells, p<0.05) Exercise showed no effect on Nur77+ activation status of the these lymphocytes, although percentage changes were +248% vs. -41% and +206% vs. -7% for CTLs and Th cell positive frequency for Nur77, respectively, for CON vs. EX from PRE to POST. Exercise caused a greater increase in Granzyme B (GZB)+ CTLs (+6%) when compared to the control group (+0.5%), and there was a greater yet non-significant percentage change of perforin expressing CTLs and NK cells in the CON group (-16 to -19%) compared to the exercising subjects (-0.5 to -5%). Discussion: Immune modulation remains a major target of interest to fight cancer using novel pharmaceutical and lifestyle interventions such as exercise. This dissertation study suggests that exercise may not be able to fully normalize but rather maintain certain peripheral immune cell frequencies and characteristics, offset the expansion of immunosuppressive cells, and potentially lower systemic inflammation levels. In conclusion, 12-weeks of exercise-based rehabilitation may positively alter some circulating immune cells and at least partially normalize the peripheral anticancer immune profile in BC patients undergoing treatment.
