Exercise Preconditioning Preserves Cardiac Function and Enhances Cardiac Recovery Following Dobutamine Stimulation in Doxorubicin-Treated Rat Hearts.

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 with the ß1-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). SED+DOX also showed a lower baseline and recovery LVDP than WR+DOX (83 ± 12 vs. 109 ± 6 mmHg baseline, 76 ± 11 vs. 100 ± 10 mmHg recovery, p<0.05). WR+DOX showed higher dP/dtmax and lower dP/dtmin when compared to SED+DOX during DOB infusion (7311 ± 1481 vs. 5167 ± 1436 mmHg/s and -4059 ± 1114 vs.-3158 ± 1176 mmHg/s, respectively). SED+DOX dP/dtmax was significantly lower during baseline and during recovery when compared to all other groups (p<0.05). These data suggest that exercise preconditioning preserved cardiac function after DOX exposure even when the heart is challenged with DOB, and it appeared to preserve the heart's ability to recover from this functional challenge.

Th17, Th22, and Myeloid-Derived Suppressor Cell Population Dynamics and Response to IL-6 in 4T1 Mammary Carcinoma.

Immunotherapies relying on type 1 immunity have shown robust clinical responses in some cancers yet remain relatively ineffective in solid breast tumors. Polarization toward type 2 immunity and expansion of myeloid-derived suppressor cells (MDSC) confer resistance to therapy, though it remains unclear whether polarization toward type 3 immunity occurs or has a similar effect. Therefore, we investigated the involvement of type 3 Th17 and Th22 cells and their association with expanding MDSC populations in the 4T1 mouse mammary carcinoma model. Th17 and Th22 were detected in the earliest measurable mass at d 14 and remained present until the final sampling on d 28. In peripheral organs, Th17 populations were significantly higher than the non-tumor bearing control and peaked early at d 7, before a palpable tumor had formed. Peripheral Th22 proportions were also significantly increased, though at later times when tumors were established. To further address the mechanism underlying type 3 immune cell and MDSC recruitment, we used CRISPR-Cas9 to knock out 4T1 tumor production of interleukin-6 (4T1-IL-6-KO), which functions in myelopoiesis, MDSC recruitment, and Th maturation. While 4T1-IL-6-KO tumor growth was similar to the control, the reduced IL-6 significantly expanded the total CD4+ Th population and Th17 in tumors, while Th22 and MDSC were reduced in all tissues; this suggests that clinical IL-6 depletion combined with immunotherapy could improve outcomes. In sum, 4T1 mammary carcinomas secrete IL-6 and other factors, to polarize and reshape Th populations and expand distinct Th17 and Th22 populations, which may facilitate tumor growth and confer immunotherapy resistance.

Moderate Intensity Endurance and Resistance Exercise Attenuates Cachexia in Tumor-bearing Mice.

BACKGROUND/AIM: Cancer cachexia encompasses several deleterious physiological alterations associated with functional impairments, poor quality of life, and increased mortality. The aim of this study was to examine the effects of chronic moderate intensity exercise training on markers of cachexia. MATERIALS AND METHODS: Balb/c mice were randomly assigned to sedentary (SED) or exercise (EX) groups and EX mice were further randomly assigned to one of three exercise modalities (aerobic, resistance, combined). RESULTS: Cachexia was induced in SED animals inoculated with C26 cells, as evidenced by significant changes in numerous markers. All cachexia-related perturbations were significantly attenuated in EX versus SED animals. Systemic inflammation was significantly decreased in all EX groups, as evident by a normalization of spleen mass and plasma IL-6. CONCLUSION: Multiple moderate intensity exercise modalities can provide significant benefits in cachectic mice, and this may be due, at least in part, to decreased systemic inflammation.

Relationships between Physiological and Self-Reported Assessment of Cancer-Related Fatigue.

The purpose of this study was to evaluate the relationships between subjective, self-reported cancer related fatigue (CRF) and objective measures of muscular strength and fatigability in cancer survivors. A total of 155 cancer survivors (60 ± 13 years of age) completed a questionnaire for the assessment of CRF, along with assessments of handgrip strength, quadriceps strength and fatigability (reduced force/torque). Fatigability was measured by completing 15 maximal isokinetic contractions of the knee extensors (QFI). Spearman's rho correlation coefficients were calculated as pairwise combinations of the numerical and categorical dependent measures. Categorical variables were analyzed via nonparametric means of association. This included a 4×4 chi-square to test whether cancer stage (0-4) was independent of fatigue status (none, mild, moderate, severe) and whether cancer treatment (surgery, radiation, chemotherapy, or combinations of these) was independent of fatigue status. None of the physiological strength and fatigue measures were significantly correlated to overall perceived fatigue or any of the subscales. Cancer stage and treatment type were also not significantly related to fatigue status (likelihood ratio = .225, Cramer's V = .228; likelihood ratio = .103, Cramer's V = .369, respectively). Our results show that levels of patient reported fatigue severity were not significantly related to muscular fatigability or strength. As a result, cancer patients experiencing fatigue may benefit from following the standard exercise guidelines for cancer survivors, regardless of their levels of self-reported fatigue.

Exercise training-induced adaptations in lung cancer patients who have undergone a lobectomy.

PURPOSE: To determine the safety and effectiveness of a prescribed, individualized, 12-week exercise intervention on cardiorespiratory function, muscular strength, and quality of life in lung cancer patients who have undergone a lobectomy. In addition, we sought to compare the exercise training response of lung cancer patients who have undergone a lobectomy to a population of cancer patients with all other cancers in order to examine the specific effects of a lobectomy when compared to cancer patients at large. METHODS: Participants were referred by a physician, and upon entry, completed an exercise-based assessment and surveys to assess various quality of life measures. Participants were divided into two groups: lung cancer patients having undergone a lobectomy (LOB, n = 9) or those diagnosed with all other cancers (AOC, n = 201). Participants underwent 12 weeks of supervised exercise based on an individualized exercise prescription. Measures of cardiorespiratory function, muscular strength, and quality of life were collected prior to the intervention and after 12 weeks of exercise training. RESULTS: Significant improvements to VO2peak (p < 0.05) were seen in both groups. Significant improvements to muscular strength (p < 0.05) were seen in both groups for all measures aside from shoulder press in the LOB group. Both groups showed significant improvements to aspects of fatigue and quality of life (p < 0.05), but only the AOC group significantly improved in measures of depression (p < 0.05). CONCLUSION: Exercise-based rehabilitation is a safe and effective intervention for lung cancer survivors who have undergone a lobectomy. These individuals saw significant improvements in cardiorespiratory fitness, muscular strength, and quality of life. Although there were similarities in the pattern of these training-induced improvements for these groups, lung cancer patients undergoing a lobectomy consistently demonstrated lower absolute values when compared to patients with all other cancer diagnoses.

Kefir Is a Viable Exercise Recovery Beverage for Cancer Survivors Enrolled in a Structured Exercise Program.

PURPOSE: This study investigated the effects of 12 wk of postexercise kefir consumption in cancer survivors who have undergone chemotherapy and/or radiation therapy. METHODS: All participants were enrolled in a structured exercise training program and separated into kefir (KEF) or control (CON) treatment groups. KEF consumed 8 oz. of kefir after exercise sessions (3 d·wk-1) for 12 wk. Outcome measures included assessments for body size and composition, aerobic fitness and muscular strength, medical history, and psychological state at pre- and postintervention time points. Blood was collected and analyzed for C-reactive protein (CRP), interleukin 6 (IL-6), and lipopolysaccharide (LPS) concentrations, and LPS-stimulated whole blood IL-6 and tumor necrosis factor α production were obtained using enzyme-linked immunosorbent assays at both time points. Monocyte numbers and phenotype were obtained using flow cytometry. RESULTS: Participants (N = 24; 9 males and 15 females) were an average of 61 ± 9.9 yr old. Kefir consumption was associated with 6.3% (P = 0.034) improvements in lean body mass, as well as 51.4% (P = 0.046), 39.3% (P = 0.017), and 64.7% (P = 0.021) improvements in measures of depression, fatigue, and gastric distress, respectively. KEF also experienced a significant 35.4% (P = 0.01) reduction in circulating LPS along with an 18.0% increase (P < 0.001) in classical monocytes % and a 22.3% decrease (P = 0.04) in nonclassical monocytes %. There were no significant changes in any other variables. CONCLUSION: Twelve weeks of kefir consumption improved lean body mass, depression, fatigue, gastric distress, and a biomarker of gut dysbiosis. Kefir improved overall and classical monocyte numbers. Kefir should be considered as a component of a postexercise dietary regimen for cancer survivors.

Structured Exercise in Cancer Survivors: Is it Enough for Neural, Mental Health and Well-being?

The purpose of this cross-sectional study was to explore physical activity, depression, fatigue, and quality of life (QOL), and their relationship to brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cancer survivors enrolled in a structured exercise program. Participants were recruited into two groups: in-treatment (IT), currently receiving chemotherapy and/or radiotherapy, and out of treatment (OT), not undergoing therapy. Participants wore accelerometers for 7 days and completed cardiorespiratory fitness, muscular strength, and depression, fatigue, and QOL assessments. Circulating BDNF and NGF concentrations were obtained using enzyme-linked immunosorbent assays. Thirty-two participants (IT: n = 13, OT: n = 19) with an average age of 63 years and BMI of 27.5, spent 78% of their waking hours engaged in sedentary behavior outside of exercise training. Significant correlations were observed between light physical activity (LPA) outside of exercise training and QOL in IT (r = 0.626, p = 0.030), and fatigue in OT (r = 0.553, p = 0.021). Moderate to vigorous physical activity (MVPA) outside of exercise training significantly correlated with leg press strength (r = 0.700, p = 0.008) in IT, and cardiorespiratory fitness (r = 0.440, p = 0.013) when groups were combined. Concentrations of NGF did not differ between groups, and in IT, BDNF was positively related to LPA outside of training and was significantly lower (87 ± 28.5 pg/mL) than in OT (137 ± 54 pg/mL; p=0.010). While structured exercise programs should focus on improving cardiorespiratory fitness and muscular strength during exercise training, these programs should consider physical activity outside of training, if well-tolerated, to potentially further lower fatigue and improve QOL in cancer survivors.

Exercise training improves postural steadiness in cancer survivors undergoing chemotherapy.

BACKGROUND: Cancer and cancer treatments negatively affect somatosensory, vestibular, and visual inputs that regulate postural stability and balance, increasing the risk of falling. Exercise training has been shown to mitigate other negative side effects of cancer treatments, such as reducing peripheral neuropathy. RESEARCH QUESTION: How does 12 weeks of supervised exercise training influence postural stability in cancer survivors who receive chemotherapy? METHODS: Postural stability of cancer survivors (n = 25; mass = 79.0 ± 22.6 kg; height = 1.66 ± 0.08 m; age = 61 ± 10 years) receiving chemotherapy was assessed prior to and following a 12-week individualized exercise training program by quantifying changes in center of pressure data. A series of 2-factor (pre/post x condition) analysis of variance with repeated measures were used to identify differences between conditions and pre- and post- training program on time and frequency domain measures. RESULTS: Mediolateral root mean square excursion (p = 0.040; es = 0.20) and resultant mean frequency (p = 0.044; es = 0.29) of the center of pressure trajectory were found to be significantly different between pre- and post-training program. Further, participants dealt better with perturbations after completing the training program by reducing mediolateral root mean square excursion and 95 % confidence ellipse when visual stimulus was removed. SIGNIFICANCE: Supervised exercise training in cancer patients undergoing chemotherapy improves postural stability in the mediolateral direction. Given that mediolateral movement of the center of pressure has previously been associated with fallers in other populations, exercise training during cancer treatments may be beneficial.

Physical activity delays accumulation of immunosuppressive myeloid-derived suppressor cells.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are potent suppressors of immune function and may play a key role in the development and progression of metastatic cancers. Aerobic exercise has been shown to have anticancer effects, yet the mechanisms behind this protection are largely unknown. Therefore, we examined the effects of physical activity on MDSC accumulation and function. METHODS: Female BALB/c mice were assigned to one of two primary groups: sedentary tumor (SED+TUM) or wheel run tumor (WR+TUM). After 6 weeks of voluntary wheel running, all animals were randomly subdivided into 4 different timepoint groups; 16, 20, 24, and 28 days post-tumor injection. All mice were inoculated with 4T1 mammary carcinoma cells in the mammary fat pad and WR groups continued to run for the specified time post-injection. Spleen, blood, and tumor samples were analyzed using flow cytometry to assess proportions of MDSCs. RESULTS: Cells expressing MDSC biomarkers were detected in the spleen, blood, and tumor beginning at d16. However, since there was no evidence of immunosuppressive function until d28, we refer to them as immature myeloid cells (IMCs). Compared to SED+TUM, levels of IMCs in the spleen were significantly lower (p < 0.05) in WR+TUM at day 16 (33.0 ± 5.2%; 23.1 ± 10.2% of total cells, respectively) and day 20 (33.9 ± 8.1%; 24.3 ± 5.1% of total cells, respectively). Additionally, there were fewer circulating IMCs in WR+TUM at day 16 and MDSC levels were significantly lower (p < 0.05) in the tumor at day 28 in WR+TUM. Additionally, a non-significant 62% and 26% reduction in metastatic lung nodules was observed at days 24 and 28, respectively. At day 28, MDSCs harvested from SED+TUM significantly suppressed CD3+CD4+ T cell proliferation (3.2 ± 1.3 proliferation index) while proliferation in WR+TUM MDSC co-cultures (5.1 ± 1.7 proliferation index) was not different from controls. CONCLUSIONS: These findings suggest that physical activity may delay the accumulation of immunosuppressive MDSCs providing a broader window of opportunity for interventions with immunotherapies.

Effects of Aerobic and Flexibility Training on Physiological and Psychosocial Function in a Patient with Anaplastic Oligodendroglioma: A Case Report.

OBJECTIVE: Diagnoses of anaplastic oligodendrogliomas are rare. For cancer rehabilitation practitioners, anaplastic oligodendroglioma may impact on the development and maintenance of prescriptive exercise. Exercise interventions for healthy individuals and cancer patients have been shown to increase functional capacity, psychosocial functioning, and aspects of cognitive function. However, there is a lack of research into exercise interventions among patients with anaplastic oligodendroglioma. This case report of a patient with anaplastic oligodendroglioma, measures the effects of aerobic and flexibility training on physiological, psychosocial, and cognitive functioning. PATIENT: A 44-year old woman diagnosed with class III anaplastic oligodendroglioma with 1p19q genetic co-deletion underwent left-frontal craniotomy, chemotherapy, and radiation treatment. Comprehensive physical, psychosocial, and cognitive assessments were completed before and after a 36-session exercise intervention. RESULTS: Following the intervention improvements were observed in 9 of the 14 physiological measures. Fatigue decreased by 20% and quality of life increased by almost 70%. Improvements were also observed in 6 of the 12 cognitive assessment variables. CONCLUSION: The 36 sessions of aerobic and flexibility training were well-tolerated by the subject. The results demonstrate the feasibility and importance of aerobic and flexibility training for the attenuation of cancer-related decrements in physiological and psychosocial variables in patients with anaplastic oligodendroglioma. The effects on cognitive function were uncertain.

Effects of Calorie Restriction and Voluntary Exercise on Doxorubicin-Induced Cardiotoxicity.

INTRODUCTION: Doxorubicin (DOX) is a widely used chemotherapeutic agent with known cardiotoxic properties, while calorie restriction (CR) and exercise have well-documented cardioprotective effects. No studies have investigated the effects of CR alone or the combined effects of CR and exercise on DOX cardiotoxicity. METHODS: Rats were divided into 4 groups based on their food intake (ad libitum or CR) and activity (sedentary or voluntary wheel running [WR]). After completing a 16-week treatment, animals received either DOX (15 mg/kg) or saline (SAL) and cardiac function was measured 5 days after treatment. Chromatography was used to quantify left ventricular DOX accumulation. RESULTS: Left ventricular developed pressure (LVDP), end systolic pressure (ESP), and left ventricular maximal rate of pressure development (dP/dtmax) were significantly higher in the CR + DOX group when compared with DOX. Fractional shortening, LVDP, ESP, dP/dtmax, and dP/dtmin were significantly higher in the CR + WR + DOX group compared with the DOX group. In addition, the CR + WR + DOX group showed significantly higher LVDP and ESP compared with the WR + DOX group. DOX accumulation in the heart was 5-fold lower ( P < .05) in the CR + WR + DOX group compared with the DOX group. CONCLUSION: This is the first study to demonstrate that CR can reduce cardiac DOX accumulation, and confirms the protective role of CR against DOX-induced cardiac dysfunction. Our data also show that combining a known cardioprotective intervention, exercise training, with CR results in additive benefits in the protection against DOX cardiotoxicity.

Cardiorespiratory fitness, visceral fat, and body fat, but not dietary inflammatory index, are related to C-reactive protein in cancer survivors.

BACKGROUND: The control of chronic inflammation has emerged as a target for improving the health of cancer survivors (CS). AIM: To examine differences in fitness and dietary characteristics of CS when grouped by low vs. moderate to high serum C-reactive protein (CRP). METHODS: CS (N = 26, mean age = 68 ± 12 years) were evaluated for body mass index (BMI), body composition, cardiorespiratory fitness, dietary intake, dietary inflammatory index (DII), and serum CRP. Participants were assigned to one of two groups based on serum CRP concentrations: low CRP (≤1 mg/L) (LWC; n = 13) or moderate to high (CRP > 1 mg/L) (MHC; n = 13) and t-tests compared them. Data are presented as mean ± SD. RESULTS: LWC had higher VO2peak values (mL/kg/min) (p = 0.0003), and lower visceral fat area (cm2) (p = 0.02) and body fat mass (kg) (p = 0.04). Secondary analysis using Pearson's correlation coefficients, including all current study participant data, found significant negative relationships between CRP and total dietary fat intake (p = 0.02), saturated fat (p = 0.03), and polyunsaturated fat (p = 0.03). CONCLUSION: CS with moderate to high serum CRP concentrations had higher fat mass, visceral fat mass, and lower cardiorespiratory fitness. There was a significant negative relationship between dietary, fat, polyunsaturated and saturated fat, and CRP. However, these dietary fat related findings warrant further investigation. To summarize, improving cardiorespiratory fitness, maintaining lower body fat, may be helpful in altering chronic inflammation in CS.

Validation of the 6-min Walk Test for Predicting Peak V˙O2 in Cancer Survivors.

PURPOSE: To assess the quality of the relationship between V˙O2peak estimated from patient outcomes on the 6-min walk test (6MWT) and the V˙O2peak calculated from patient outcomes on the University of Northern Colorado Cancer Rehabilitation Institute (UNCCRI) treadmill protocol. METHODS: Cancer survivors (N = 187) completed the UNCCRI treadmill protocol and a 6MWT 1 wk apart in randomized order to obtain V˙O2peak. Values from the UNCCRI treadmill protocol were compared against four common 6MWT V˙O2peak prediction equations. RESULTS: All four 6MWT prediction equations significantly (P < 0.001) underestimated V˙O2peak with predicted values ranging from 8.0 ± 4.1 mL·kg·min to 18.6 ± 3.1 mL·kg·min, whereas the UNCCRI treadmill protocol yielded a significantly higher value of 23.9 ± 7.6 mL·kg·min. A positive strong correlation occurred between estimated V˙O2peak derived from the UNCCRI treadmill protocol and only one of the V˙O2peak values derived from the 6MWT prediction equations (r = 0.81), and all four equations consistently underpredicted V˙O2peak. CONCLUSIONS: These findings suggest that the 6MWT is not a valid test for predicting V˙O2peak in the cancer population due to its consistent underestimation of V˙O2peak regardless of the prediction equation. Obtaining an accurate and valid V˙O2peak value is necessary to correctly prescribe an individualized exercise rehabilitation regimen for cancer survivors. It is recommended that clinicians avoid the 6MWT and instead implement treadmill testing to volitional fatigue to quantify V˙O2peak in cancer survivors.

Effects of an Exercise Intervention on Cancer-Related Fatigue and Its Relationship to Markers of Oxidative Stress.

BACKGROUND: Although the underlying mechanisms of cancer-related fatigue (CRF) are not fully characterized, treatment-associated oxidative stress may play a role. The purpose of this study was to determine the effect of an exercise intervention on the relationship between CRF and oxidative stress. METHODS: Upon cessation of radiation or chemotherapy, 8 cancer patients participated in a 10-week exercise intervention (EX), while 7 continued standard care (CON). Blood draws and fatigue questionnaires were administered to cancer patients before and after the intervention as well as to 7 age-matched individuals with no cancer history. Changes in plasma 8-hydroxy-deoxyguanosine (8-OHdG), protein carbonyls, antioxidant capacity, and fatigue were compared between groups. Correlations between CRF and oxidative stress were evaluated. RESULTS: Mean total fatigue scores decreased significantly (5.0 ± 2.2 to 2.6 ± 1.5, P < .05) in EX, but not in CON. Antioxidant capacity significantly increased (+41%; P < .05) and protein carbonyls significantly decreased (-36%; P < .05) in EX, but not in CON. Increases in antioxidant capacity were significantly correlated with reductions in affective ( r = -.49), sensory ( r = -.47), and cognitive fatigue ( r = -.58). Changes in total ( r = .46) and affective ( r = .47) fatigue exhibited significant correlations with changes in 8-OHdG over time, while behavioral ( r = .46) and sensory ( r = .47) fatigue changes were significantly correlated with protein carbonyls. CONCLUSIONS: Oxidative stress may be implicated in CRF, while improved antioxidant capacity following an exercise intervention may play a role in mitigating CRF in cancer survivors.

Effects of Resistance Exercise Training on Doxorubicin-Induced Cardiotoxicity.

Although highly effective, doxorubicin (DOX) use is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether resistance training (RT) would protect against DOX-induced cardiac dysfunction and determine whether any observed functional preservation is a result of reduced lipid peroxidation or a preservation of the cardiac myosin heavy chain (MHC) isoform distribution. Rats were resistance-trained or remained sedentary for 12 weeks, then treated with 12.5 mg/kg DOX or 0.9% saline. Five days after DOX exposure, cardiac function, lipid peroxidation, and MHC isoform expression were quantified. RT preserved cardiac function and attenuated the α-to ß-MHC shift that occurs with DOX treatment. No significant differences in lipid peroxidation were observed between sedentary and RT animals treated with DOX. These data suggest that resistance-type exercise can provide protection against DOX-induced cardiac dysfunction, which may be a result of a preservation of the cardiac MHC isoform distribution.

Feasibility of a combined aerobic and cognitive training intervention on cognitive function in cancer survivors: a pilot investigation.

BACKGROUND: Cancer-related cognitive impairment (CRCI) may negatively affect upwards of 75% of cancer patients. Exercise and cognitive training, independently, may increase functional capacity and aspects of cognitive function. Yet, combined training protocols have not been evaluated in cancer survivor populations. Therefore, the aim of this study was to explore the feasibility of a quasi-randomized, controlled, exploratory, repeated-measures aerobic and cognitive training intervention on cognitive function in participants undergoing treatment for cancer (N = 28). METHODS: Pre- and post-physical and cognitive assessments were administered. A 36-session (approximately 12 weeks) computer-based cognitive (COG), aerobic (AER), cognitive and aerobic (AER + COG), and flexibility (CON) training intervention was completed. Dependent measures t tests and pre- to post percentages were then calculated to address within-group changes for each dependent variable. RESULTS: Within-group measures revealed that the AER logical memory scores (pre- to post mean difference [2.3], 95.0% CI [0.9, 3.7], percentage change [32.7%]), delayed recall scores (pre- to post mean difference [2.1], 95.0% CI [0.3, 3.9], percentage change [27.2%]), block design scores (pre- to post mean difference [1.7], 95.0% CI [0.2, 3.2], percentage change [19.0%]), and letter-number sequencing scores (pre- to post mean difference [1.0], 95.0% CI [0.2, 1.8], percentage change [12.3%]) all increased. Aspects of verbal fluidity scores increased in the CON group. However, all cognitive scores (AER + COG and COG groups) failed to increase. CONCLUSIONS: Aerobic training for CRCI may positively impact cognitive function. Individually, these methods may appropriately address CRCI, but combined training of this nature may be too demanding for patients undergoing treatment for cancer. However, larger randomized trials are needed to substantiate this protocol in large-scale cancer rehabilitation centers.

Exercise Protects against Cancer-induced Cardiac Cachexia.

Cancer has been shown to negatively stimulate autophagy, leading to a decline in cardiac function. Although exercise is cardioprotective, its influence over autophagy-mediated tumor growth and cardiac function are not well defined. PURPOSE: This study aimed to determine the effect of exercise on tumor morphology and cardiac function. METHODS: Fisher 344 rats (n = 28) were assigned to one of four groups: 1) sedentary non-tumor bearing (SED), 2) sedentary tumor bearing (SED + T), 3) wheel run non-tumor bearing (WR), or 4) wheel run tumor bearing (WR + T). Rats remained sedentary or exercised for 6 wk. At week 4, rats in tumor groups were inoculated with MatBIII tumor cells. At week 6, cardiac function was measured. RESULTS: SED + T animals exhibited significantly lower left ventricular developed pressure when compared with SED, WR, and WR + T (P < 0.05). This coincided with a significant increase in cardiac autophagy (increased LC3-II) in SED + T animals when compared with SED, WR, and WR + T (P < 0.05). Furthermore, SED + T hearts showed a significant increase in ß-myosin heavy chain expression versus nontumor groups (P < 0.05). Tumor mass was significantly larger (P < 0.001) in SED + T animals when compared with WR + T animals, which was accompanied by a significant increase in tumor LC3-II protein expression (P < 0.05). CONCLUSION: Nonexercised tumor-bearing rats showed severe cardiac dysfunction and excessive, maladaptive autophagy in the heart and tumors. Voluntary exercise preserved cardiac function and attenuated the autophagic response in heart and tumor tissues. This preservation may be related to the reduced tumor growth in aerobically exercised rats, to the improved regulation of autophagy by exercise, or both.

Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia.

PURPOSE OF REVIEW: Cancer cachexia remains understudied and there are no standard treatments available despite the publication of an international consensus definition and the completion of several large phase III intervention trials in the past 6 years. In September 2015, The University of Rochester Cancer Center NCORP Research Base led a Symposium on Cancer Cachexia and Sarcopenia with goals of reviewing the state of the science, identifying knowledge gaps, and formulating research priorities in cancer cachexia through active discussion and consensus. RECENT FINDINGS: Research priorities that emerged from the discussion included the implementation of morphometrics into clinical decision making, establishing specific diagnostic criteria for the stages of cachexia, expanding patient selection in intervention trials, identifying clinically meaningful trial endpoints, and the investigation of exercise as an intervention for cancer cachexia. SUMMARY: Standardizing how we define and measure cancer cachexia, targeting its complex biologic mechanisms, enrolling patients early in their disease course, and evaluating exercise, either alone or in combination, were proposed as initiatives that may ultimately result in the improved design of cancer cachexia therapeutic trials.

Marijuana use and inpatient outcomes among hospitalized patients: analysis of the nationwide inpatient sample database.

The purpose of this paper is to examine the relationship between marijuana use and health outcomes among hospitalized patients, including those hospitalized with a diagnosis of cancer. A total of 387,608 current marijuana users were identified based on ICD-9 codes for marijuana use among hospitalized patients in the Nationwide Inpatient Sample database between 2007 and 2011. Logistic regression analysis was performed to determine the association between marijuana use and heart failure, cardiac disease, stroke, and in-hospital mortality. All models were adjusted for age, gender, race, residential income, insurance, residential region, pain, and number of comorbidities. Among hospitalized patients, marijuana use was associated with a 60% increased odds of stroke (OR: 1.60, 95% CI: 1.44-1.77) compared with non-users, but significantly reduced odds of heart failure (OR: 0.78, 95% CI: 0.75-0.82), cardiac disease (OR: 0.86, 95% CI: 0.82-0.91), or in-hospital mortality (OR: 0.41, 95% CI: 0.38-0.44). Among cancer patients, odds of in-hospital mortality was significantly reduced among marijuana users compared with non-users (OR: 0.44, 95% CI: 0.35-0.55). Hospitalized marijuana users were more likely to experience a stroke compared with non-users, but less likely to experience in-hospital mortality. Prospective studies will be needed to better characterize the health effects of marijuana use, especially among older, sicker, and/or hospitalized patients. In the meantime, conversations regarding marijuana use/misuse may be warranted in the clinical setting in order for patients and healthcare providers to adequately weigh the anticipated benefits of marijuana use with potentially significant health risks.

Effects of Exercise on Doxorubicin-Induced Skeletal Muscle Dysfunction.

INTRODUCTION: Chemotherapy treatment with doxorubicin (DOX) can have a negative effect on normal skeletal muscle function. Recent research demonstrates the potential value of exercise in alleviating DOX-induced cardiotoxicity. Yet up to now, little research has been done to examine whether exercise might also be effective in addressing DOX's skeletal muscle adverse effects, especially because posttreatment skeletal muscle dysfunction may cause patient difficulties with completing activities of daily living. The main aim of this study was to examine how resistance training (RT) and treadmill (TM) training play a role in preventing DOX-induced skeletal muscle dysfunction. METHODS: Male Sprague-Dawley rats were randomly placed into an RT, TM, or sedentary (SED) group for 10 wk and then received either a bolus injection of DOX (15 mg·kg) or saline as a control. Skeletal muscle function was then assessed ex vivo 5 d after injection. RESULTS: SED animals treated with DOX showed significantly lower maximal twitch force, maximal rate of force production, and maximal rate of force decline versus SED + saline in the soleus (SOL) (Type I muscle). In the extensor digitorum longus (Type II muscle), treatment with DOX resulted in a significantly lower maximal rate of force production and maximal rate of force decline. RT preserved maximal twitch force and maximal rate of force decline in the SOL. TM attenuated DOX-induced fatigue in the SOL but not in the extensor digitorum longus. CONCLUSION: These findings suggest that RT and TM before DOX could be useful in preserving skeletal muscle function and minimizing fatigue after chemotherapy, but this protection may be dependent on the skeletal muscle type.