Publications by authors named "Po-Ju Lin"

37 Publications

Physical Activity Patterns and Relationships With Cognitive Function in Patients With Breast Cancer Before, During, and After Chemotherapy in a Prospective, Nationwide Study.

J Clin Oncol 2021 10 18;39(29):3283-3292. Epub 2021 Aug 18.

Department of Surgery, University of Rochester Medical Center, Rochester, NY.

Purpose: Physical activity (PA) is a promising intervention for cancer-related cognitive decline, yet research assessing its use during chemotherapy is limited. This study evaluated patterns of PA before, during, and after chemotherapy in patients with breast cancer and the association between PA and cognitive function.

Methods: In a nationwide, prospective cohort study, we assessed PA (Aerobics Center Longitudinal Study PA measure) and perceived and objectively measured cognitive functioning (Functional Assessment of Cancer Therapy-Cognitive, Delayed Match to Sample, and Rapid Visual Processing measures) at prechemotherapy (T1), postchemotherapy (T2), and 6 months postchemotherapy (T3) in patients with breast cancer and cancer-free, age-matched controls at equivalent time points. Longitudinal linear mixed-effects models (LMMs) characterized PA changes over time between patients and controls, adjusting for demographic and clinical factors. LMMs further estimated the role of prechemotherapy PA and changes in PA during chemotherapy on cognitive changes over time.

Results: Patients with stage I-IIIC breast cancer (n = 580; age M [standard deviation] = 53.4 [10.6] years) and controls (n = 363; age M [standard deviation] = 52.6 [10.3] years) were included. One third of patients met national PA guidelines at T1, dropping to 21% at T2 before rising to 37% at T3. LMMs revealed declines in PA from T1 to T2 in patients compared with controls (all < .001). Patients meeting guidelines at T1 demonstrated better cognitive scores over time on the Functional Assessment of Cancer Therapy-Cognitive and Rapid Visual Processing (all < .05), with similar patterns of objectively-measured cognitive function as controls. In patients, greater moderate-to-vigorous PA at the previous time point was significantly associated with better cognitive trajectories (all < .05), and adherence to PA guidelines throughout chemotherapy was associated with better self-reported cognition ( .01).

Conclusion: This nationwide study demonstrates that PA maintenance before and during chemotherapy is associated with better cognitive function immediately and 6 months after chemotherapy completion.
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http://dx.doi.org/10.1200/JCO.20.03514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500586PMC
October 2021

Low cardiac dose and neutrophil-to-lymphocyte ratio predict overall survival in inoperable esophageal squamous cell cancer patients after chemoradiotherapy.

Sci Rep 2021 03 23;11(1):6644. Epub 2021 Mar 23.

Department of Radiation Oncology, Changhua Christian Hospital, Changhua, 500, Taiwan.

We aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010-2015, we identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval [CI]: 10.38-15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio [HR] 3.12, 95% CI 1.30-7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26-3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39-4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12-3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.
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http://dx.doi.org/10.1038/s41598-021-86019-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988072PMC
March 2021

Developing and adapting a mobile health exercise intervention for older patients with myeloid neoplasms: A qualitative study.

J Geriatr Oncol 2021 07 4;12(6):909-914. Epub 2021 Mar 4.

James P. Wilmot Cancer Institute, Rochester, NY, USA; Division of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA. Electronic address:

Introduction: Older patients with myeloid neoplasms (MN) receiving outpatient chemotherapy are at risk of experiencing treatment-related toxicities such as functional decline. A mobile health (mHealth) exercise intervention may ameliorate these toxicities. This qualitative study aimed to inform the design of a mHealth exercise intervention for this population.

Methods: This was a qualitative study of thirteen patients aged ≥60 years receiving hypomethylating agents for MN. EXCAP©® is a home-based walking and progressive resistance exercise program. We combined EXCAP©® with a mobile app; the combination (GO-EXCAP Mobile App) has not been previously tested. A brief verbal description about the intervention was provided to the participants but they did not perform it. Participants were interviewed and inductive thematic analysis was used to analyze the data.

Results: Mean age was 71.6 (SD 8.5). Three themes were identified: 1) Perceptions of the intervention feasibility, 2) Ways to leverage the app to deliver the exercise intervention, and 3) Personalized exercise goals. Walking and resistance exercises were perceived to be feasible. Patients were comfortable initiating the intervention in cycle 2 of chemotherapy, with exercise increments occurring from week 2-4 of the cycle. Ways to leverage the app to deliver EXCAP©® include 1) Video feature for exercise demonstration and interactions, and 2) Exercise data and symptom surveys to be communicated to the exercise physiologist and primary oncology team. Preservation of existing function and activity was an important goal to participants.

Conclusions: Our findings provide insights about the preferences of older adults with MN for a mHealth exercise intervention.
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http://dx.doi.org/10.1016/j.jgo.2021.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260435PMC
July 2021

Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy.

Sci Rep 2021 01 27;11(1):2377. Epub 2021 Jan 27.

Cardiovascular Division, Institute of Biomedical Science, Academia Sinica, National Taiwan University College of Medicine, 128 Academia Road, Sec. 2, Nankang, Taipei, 115, Taiwan.

MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.
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http://dx.doi.org/10.1038/s41598-021-81700-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840921PMC
January 2021

Effects of High-Dose Vitamin D Supplementation on Phase Angle and Physical Function in Patients with Prostate Cancer on ADT.

Nutr Cancer 2021 11;73(10):1882-1889. Epub 2020 Sep 11.

Department of Surgery, University of Rochester Medical Center (URMC), Rochester, New York, USA.

Purpose: Androgen deprivation therapy (ADT) is commonly used to treat patients with advanced prostate cancer but is associated with functional decline. Bioelectrical impedance analysis (BIA)-derived phase angle may reflect frailty and functional decline in cancer patients. High-dose vitamin D supplementation may improve phase angle values and physical function.

Methods: We conducted an exploratory analysis from a phase II randomized controlled trial investigating the efficacy of high-dose vitamin D supplementation in prostate cancer patients (age ≥ 60 yrs). Fifty-nine patients were randomized to high-dose vitamin D (600 IU/day plus 50,000 IU/week) or low-dose: RDA for vitamin D (600 IU/day plus placebo weekly) for 24 weeks. Phase angle was measured by BIA. Physical function measures included handgrip strength, 6-minute walk test, Short Performance Physical Battery and leg extension. All testing was completed at baseline, week 12 and week 24.

Results: Phase angle values were wider over the entire study in the high-dose vitamin D arm indicating healthier muscle cells. The low-dose vitamin D arm had phase angle values consistent with frailty cutoffs in older men (<5.7°).

Conclusion: Patients in the high-dose vitamin D arm experienced wider phase angle values over the course of the study which may indicate less frailty. ClinicalTrials.gov ID: NCT02064946.
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http://dx.doi.org/10.1080/01635581.2020.1819348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947019PMC
October 2021

Excess Body Weight and Cancer-Related Fatigue, Systemic Inflammation, and Serum Lipids in Breast Cancer Survivors.

Nutr Cancer 2021 19;73(9):1676-1686. Epub 2020 Aug 19.

Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY, USA.

Background: Cancer-related fatigue (CRF) is a common side effect impacting breast cancer survivors. Research points to a relationship between obesity and CRF in breast cancer survivors related to elevated systemic inflammation and metabolic alterations.

Methods: This cross-sectional study examined the relationship of obesity to CRF, inflammatory markers and serum lipids through a secondary analysis of a nationwide randomized controlled trial. Breast cancer survivors with CRF were categorized based on BMI category. Symptoms of CRF, inflammatory markers and serum fatty acids were assessed among groups.

Results: There were 105 breast cancer survivors in the analysis. BMI was positively associated with CRF based on MFSI General ( = 0.020; 95% C.I. 0.024, 0.273) and MFSI Physical ( = 0.013; 95% C.I. 0.035, 0.298) subscales. TNF-α ( = 0.007; 95% C.I. 0.007, 0.044), and IL-6 ( = 0.020; 95% C.I. 0.006, 0.073) were elevated in the obese. Monounsaturated fatty acid levels ( = 0.047; 95% C.I. 0.000, 0.053) and the omega-6 to omega-3 fatty acid ratio were associated with obesity ( = 0.047; 95% C.I. 0.002, 0.322).

Conclusions: Obese breast cancer survivors had greater levels of CRF, inflammatory markers and certain fatty acids. Inflammatory markers and fatty acids were not found to have any mediating or positive association with CRF variables in this analysis. NCT02352779.
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http://dx.doi.org/10.1080/01635581.2020.1807574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904100PMC
September 2021

Survival impacts of different nodal characteristics and T-classification in N3 nasopharyngeal carcinoma patients.

Oral Oncol 2020 09 9;108:104820. Epub 2020 Jun 9.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Radiation Oncology, Changhua Christian Hospital, Changhua, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Objectives: We investigated the survival impacts of various nodal characteristics and T-classification on nasopharyngeal carcinoma (NPC) patients with the 8th AJCC/UICC staging criteria N3.

Materials And Methods: Pretreatment MRIs from 110 staged N3 NPC patients were reviewed. There were 23 T1, 25 T2, 32 T3, and 30 T4, respectively. All except one patient belonged to WHO type II pathology. All patients received curative radiotherapy 68.0-76.8 Gy plus different chemotherapy, including induction, concurrent, adjuvant or any combination. Various endpoints, including OS (overall survival), DFS (disease-free survival), LRFFS (locoregional failure-free survival), DMFFS (distant metastasis failure-free survival) were compared between different nodal characteristics and T-classification.

Results: There were no statistically significant differences in all analyzed survival curves between various nodal characteristics, including unilateral N3 vs. bilateral N3, "large" nodes (>6 cm) alone vs. "low" nodes (below the caudal border of cricoid cartilage) alone vs. combined "large" and "low" nodes, risk score 1 vs. 2 vs. 3 vs. 4 (by counting the sum of "large" and "low" nodes in the same case), and radiologic extra-nodal extension. Patients with T4, compared with those of T1-3 have worse OS (5-year rates, 42.2% vs. 82.8%, P < 0.0001), DFS (5-year rates, 43.9% vs. 68.9%, P = 0.0037), LRFFS (5-year rates, 69.3% vs. 82.7%, P = 0.0432), and DMFFS (5-year rates, 57.2% vs. 77.7%, P = 0.0163).

Conclusions: Our results support merging previous N3a and N3b as a N3 category in the 8th edition new staging system. Patients with T4N3 diseases have extremely poor outcome and deserve to strengthen the treatment intensity in future trials.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104820DOI Listing
September 2020

Effects of Epstein-Barr virus viral load and different treatment modality for stage III nasopharyngeal carcinoma.

Head Neck 2020 08 3;42(8):1765-1774. Epub 2020 Feb 3.

Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Background: We investigated treatment results, the effects of different treatment modality, and pretreatment Epstein-Barr virus (EBV) viral load for stage III nasopharyngeal carcinoma (NPC) patients.

Methods: The initial definitive treatment for 356 stage III NPC patients consisted of concurrent chemoradiotherapy (CCRT) or induction chemotherapy plus radiotherapy (IndCT-RT). The pretreatment EBV DNA level separated patients into a high (n = 106) or low (n = 250) viral load (≥ or < 1000 copies/mL) subgroup. Outcome measures include relapse rates and various survivals.

Results: The 5-year rates of overall survival (OS), progression-free survival (PFS), distant metastasis failure-free survival (DMFFS), and locoregional failure-free survival (LRFFS) were 88.6%, 83.0%, 90.5%, and 90.5%, respectively. Patient characteristics and pretreatment viral load between IndCT-RT and CCRT were no significant differences except for a higher percentage of N2 disease in the IndCT-RT subgroup. Both treatment modality resulted in similar relapse rates (P = .56), OS (P = .20), PFS (P = .53), DMFFS (P = .89), and LRFFS (P = .35). However, patients with a high viral load experienced a higher relapse rate (33.0% vs 12.4%, P < .001) and worse OS (5-year rate, 79.0% vs 92.8%, P < .001), PFS (73.7% vs 88.4%, P < .001), DMFFS (80.2% vs 95.0%, P < .001), and LRFFS (85.6% vs 92.6%, P = .005) than those with a low viral load.

Conclusion: Long-term treatment results for stage III NPC patients are rather good. IndCT-RT can achieve the same treatment outcome as CCRT. Risk grouping by pretreatment viral load identified a subgroup (30%) of patients associated with a significantly higher relapse rates and worse survivals. These high-risk patients need to strengthen treatment intensity in future trials.
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http://dx.doi.org/10.1002/hed.26096DOI Listing
August 2020

Hypoxia-induced H19/YB-1 cascade modulates cardiac remodeling after infarction.

Theranostics 2019 21;9(22):6550-6567. Epub 2019 Aug 21.

Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Long non-coding RNA (lncRNAs) has been identified as a pivotal novel regulators in cardiac development as well as cardiac pathogenesis. lncRNA H19 is known as a fetal gene but it is exclusively abundant in the heart and skeletal muscles in adulthood, and is evolutionarily conserved in humans and mice. It has been reported to possess a significant correlation with the risk of coronary artery diseases. However, the function of H19 is not well characterized in heart. Loss-of-function and gain-of-function mouse models with left anterior descending coronary artery-ligation surgery were utilized to evaluate the functionality of H19 . For mechanistic studies, hypoxia condition were exerted in models to mimic cardiac ischemic injury. Chromatin isolation by RNA immunoprecipitation (ChIRP) was performed to reveal the interacting protein of lncRNA H19. lncRNA H19 was significantly upregulated in the infarct area post-surgery day 4 in mouse model. Ectopic expression of H19 in the mouse heart resulted in severe cardiac dilation and fibrosis. Several extracellular matrix (ECM) genes were significantly upregulated. While genetic ablation of H19 by CRISPR-Cas9 ameliorated post-MI cardiac remodeling with reduced expression in ECM genes. Through chromatin isolation by RNA purification (ChIRP), we identified Y-box-binding protein (YB)-1, a suppressor of Collagen 1A1, as an interacting protein of H19. Furthermore, H19 acted to antagonize YB-1 through direct interaction under hypoxia, which resulted in de-repression of Collagen 1A1 expression and cardiac fibrosis. Together these results demonstrate that lncRNA H19 and its interacting protein YB-1 are crucial for ECM regulation during cardiac remodeling.
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http://dx.doi.org/10.7150/thno.35218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771230PMC
October 2020

Longitudinal assessment of the impact of higher body mass index on cancer-related fatigue in patients with breast cancer receiving chemotherapy.

Support Care Cancer 2020 Mar 2;28(3):1411-1418. Epub 2019 Jul 2.

Department of Surgery, University of Rochester Medical Center (URMC), 265 Crittenden Blvd, CU 420658, Rochester, NY, 14642, USA.

Purpose: To assess the impact of obesity on cancer-related fatigue (CRF) in patients with breast cancer, through a secondary analysis of a large, longitudinal, nationwide study of breast cancer patients beginning chemotherapy.

Methods: All patients (N = 565; aged 53 ± 10.6) with breast cancer completed the multidimensional fatigue symptom inventory and the symptom inventory to measure CRF symptoms at baseline, post-chemotherapy, and 6 months post-chemotherapy. Height and weight at baseline were used to categorize subjects based on body mass index (BMI): obese (≥ 30.0 kg/m; n = 294), overweight (25.0-29.9 kg/m; n = 146), and normal weight (18.5-24.9 kg/m; n = 125). Multivariate regression models evaluated the relationship of obesity level to CRF over time, controlling for age, menopausal status, race, Karnofsky Performance Status, cancer stage, radiation, and exercise status.

Results: At baseline, the obese had significantly higher CRF symptoms than the normal weight subjects for both the Multidimensional fatigue symptom inventory (MFSI) total (obese = 11.2 vs normal weight = 6.3; p = 0.03) and Symptom Inventory (SI) (obese = 3.5 vs normal weight = 2.9; p = 0.03). Significantly higher SI fatigue scores persisted at post-chemotherapy for the obese (obese = 5.0 vs normal weight = 4.4; p = 0.02). At 6 months post-chemotherapy, the obese patients still had significantly higher SI fatigue scores (obese = 3.5 vs normal weight = 3.0; p = 0.05).

Conclusion: Obese patients suffered greater CRF from pre-chemotherapy through 6 months post-chemotherapy. Recommendations for weight loss or weight maintenance may impact CRF levels in obese breast cancer patients before and after chemotherapy.
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http://dx.doi.org/10.1007/s00520-019-04953-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243469PMC
March 2020

Influence of Yoga on Cancer-Related Fatigue and on Mediational Relationships Between Changes in Sleep and Cancer-Related Fatigue: A Nationwide, Multicenter Randomized Controlled Trial of Yoga in Cancer Survivors.

Integr Cancer Ther 2019 Jan-Dec;18:1534735419855134

1 University of Rochester Medical Center, Rochester, NY, USA.

Background: Cancer-related fatigue (CRF) often co-occurs with sleep disturbance and is one of the most pervasive toxicities resulting from cancer and its treatment. We and other investigators have previously reported that yoga therapy can improve sleep quality in cancer patients and survivors. No nationwide multicenter phase III randomized controlled trial (RCT) has investigated whether yoga therapy improves CRF or whether improvements in sleep mediate the effect of yoga on CRF. We examined the effect of a standardized, 4-week, yoga therapy program (Yoga for Cancer Survivors [YOCAS]) on CRF and whether YOCAS-induced changes in sleep mediated changes in CRF among survivors.

Study Design And Methods: Four hundred ten cancer survivors were recruited to a nationwide multicenter phase III RCT comparing the effect of YOCAS to standard survivorship care on CRF and examining the mediating effects of changes in sleep, stemming from yoga, on changes in CRF. CRF was assessed by the Multidimensional Fatigue Symptom Inventory. Sleep was assessed via the Pittsburgh Sleep Quality Index. Between- and within-group intervention effects on CRF were assessed by analysis of covariance and 2-tailed t test, respectively. Path analysis was used to evaluate mediation.

Results: YOCAS participants demonstrated significantly greater improvements in CRF compared with participants in standard survivorship care at post-intervention ( P < .01). Improvements in overall sleep quality and reductions in daytime dysfunction (eg, excessive napping) resulting from yoga significantly mediated the effect of yoga on CRF (22% and 37%, respectively, both P < .01).

Conclusions: YOCAS is effective for treating CRF among cancer survivors; 22% to 37% of the improvements in CRF from yoga therapy result from improvements in sleep quality and daytime dysfunction. Oncologists should consider prescribing yoga to cancer survivors for treating CRF and sleep disturbance.
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http://dx.doi.org/10.1177/1534735419855134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552348PMC
December 2019

Multicenter Randomized Controlled Trial of Omega-3 Fatty Acids Versus Omega-6 Fatty Acids for the Control of Cancer-Related Fatigue Among Breast Cancer Survivors.

JNCI Cancer Spectr 2019 Jun 21;3(2):pkz005. Epub 2019 Feb 21.

Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY.

Background: Cancer-related fatigue (CRF) is a common side effect of adjuvant therapy and becomes a chronic problem for approximately one-third of survivors. Omega-3 polyunsaturated fatty acids (O3-PUFA) demonstrated preliminary antifatigue effects in previous research, but have not been investigated in fatigued cancer survivors.

Methods: Breast cancer survivors 4-36 months posttreatment with a CRF score of 4 or more of 10 using the symptom inventory (SI) were randomly assigned to O3-PUFA (fish oil, 6 g/d), omega-6 PUFA (O6-PUFA; soybean oil, 6 g/d), or a low-dose combination of O3-/O6-PUFA (3 g/d O3-PUFA and O6-PUFA) for 6 weeks. CRF was assessed by the SI (screening question), the Brief Fatigue Inventory, and the Multidimensional Fatigue Symptom Index. Protein and mRNA levels of inflammatory and antioxidant biomarkers, along with fatty acid and lipid levels, were assessed at baseline and week 6. Statistical tests were two-sided.

Results: A total of 108 breast cancer survivors consented; 97 subjects were randomly assigned and 81 completed the trial. The SI CRF score decreased by 2.51 points at week 6 with O6-PUFA and by 0.93 points with O3-PUFA, with statistically significant between-group difference (effect size = -0.86,  < .01). Similar changes were observed for the Brief Fatigue Inventory and Multidimensional Fatigue Symptom Index but were not statistically significant. Stratified analyses showed the largest benefit was observed in those with severe baseline CRF (≥7). Compared with O3-PUFA, O6-PUFA supplementation statistically significantly decreased proinflammatory markers in the TNF-α signaling pathway.

Conclusion: Contrary to our original hypothesis, O6-PUFA statistically significantly reduced CRF compared with O3-PUFA. Further research is needed to confirm these findings and to elucidate mechanisms of action.
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http://dx.doi.org/10.1093/jncics/pkz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512349PMC
June 2019

Effects of a Home-based Exercise Program on Anxiety and Mood Disturbances in Older Adults with Cancer Receiving Chemotherapy.

J Am Geriatr Soc 2019 05;67(5):1005-1011

James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.

Background/objective: Exercise interventions improve anxiety and mood disturbances in patients with cancer. However, studies are limited in older adults with cancer. We assessed the effects of exercise on anxiety, mood, and social and emotional well-being in older patients with cancer during their first 6 weeks of chemotherapy.

Design: Exploratory secondary analysis of a randomized controlled trial (RCT).

Setting: Community oncology practices.

Participants: Older patients (aged 60 years or older) undergoing chemotherapy (N = 252).

Intervention: Patients were randomized to Exercise for Cancer Patients (EXCAP) or usual care (control) for the first 6 weeks of chemotherapy. EXCAP is a home-based, low- to moderate-intensity progressive walking and resistance training program.

Measurements: Analysis of covariance, with study arm as the factor, baseline value as the covariate, and study arm × baseline interaction, was used to evaluate arm effects on postintervention anxiety (State Trait Anxiety Inventory [STAI]), mood (Profile of Mood States [POMS]), and social and emotional well-being (Functional Assessment of Cancer Therapy-General subscales) after 6 weeks.

Results: Median age was 67 years; 77% had breast cancer. Statistically significant group differences were observed in the STAI score (P = .001), POMS score (P = .022), social well-being (P = .002), and emotional well-being (P = .048). For each outcome, EXCAP patients with worse baseline scores had larger improvements at 6 weeks; these improvements were clinically significant for STAI score and social well-being.

Conclusions: Among older cancer patients receiving chemotherapy, a 6-week structured exercise program improved anxiety and mood, especially among those participants with worse baseline symptoms. Additional RCTs are needed to confirm these findings and evaluate the appropriate exercise prescription for managing anxiety, mood, and well-being in this patient population. J Am Geriatr Soc 67:1005-1011, 2019.
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http://dx.doi.org/10.1111/jgs.15951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544022PMC
May 2019

Effectiveness of exercise-based rehabilitation on functional capacity and quality of life in head and neck cancer patients receiving chemo-radiotherapy.

Support Care Cancer 2019 Oct 27;27(10):3913-3920. Epub 2019 Mar 27.

Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center School of Medicine and Dentistry, Rochester, New York, USA.

Purpose: Fatigue, decreased functionality, and impaired quality of life are some of the most common adverse outcomes of chemo-radiotherapy (CRT). Head and neck cancers (HNC) affect more than half a million individuals globally and its treatment takes a heavy toll on the patient, often affecting their speech, swallowing, and respiratory functions, and as a result they often develop fatigue, depression, and physical inactivity. The purpose of this study was to evaluate the effectiveness of exercise-based rehabilitation on functional capacity, quality of life, fatigue, hemoglobin, and platelet counts in patients with HNC on CRT.

Patients And Methods: A randomized controlled trial was conducted on 148 patients with head and neck cancer undergoing CRT to evaluate the effectiveness of exercise on functional capacity measured by the 6-min walk test, quality of life measured by the Medical Outcomes Survey Short Form 36 v2 questionnaire, fatigue by the NCCN (0-10) scale, hemoglobin, and platelets. The control group received standard physical activity recommendations while the exercise group received a structured exercise program of aerobic and active resistance exercises for a period of 11 weeks.

Results: There was a significant improvement in the functional capacity (p < 0.001), quality of life (p < 0.001), and prevention of worsening of fatigue (p < 0.001) in the exercise group. The blood parameters did not show a significant difference between the control group and the exercise group.

Conclusion: Our results elucidate that an 11-week structured exercise program for HNC patients receiving CRT helps in improving their functional capacity and quality of life. It also prevents deterioration of fatigue levels in the exercise group.
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http://dx.doi.org/10.1007/s00520-019-04750-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728220PMC
October 2019

Nutritional Interventions for Treating Cancer-Related Fatigue: A Qualitative Review.

Nutr Cancer 2019 26;71(1):21-40. Epub 2019 Jan 26.

a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA.

Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary intake prior to, during, and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger, or probiotics may improve cancer survivors' energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.
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http://dx.doi.org/10.1080/01635581.2018.1513046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456409PMC
May 2020

Systematic Review of Randomized Controlled Trials of Exercise Interventions Using Digital Activity Trackers in Patients With Cancer.

J Natl Compr Canc Netw 2019 01;17(1):57-63

Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50-70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients' step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all 05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.
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http://dx.doi.org/10.6004/jnccn.2018.7082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519727PMC
January 2019

Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair.

Circulation 2019 01;139(5):647-659

Program in Molecular Medicine, National Yang Ming University and Academia Sinica, Taipei, Taiwan (T.W.H.T., P.C.C.H.).

Background: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.

Methods: To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.

Results: Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.

Conclusions: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035235DOI Listing
January 2019

Exercise for Toxicity Management in Cancer-A Narrative Review.

Oncol Hematol Rev 2018 15;14(1):28-37. Epub 2018 Feb 15.

University of Rochester Medical Center, James P Wilmot Cancer Institute, Rochester, NY, US.

Although the treatment of cancer is more effective now than ever, patients with cancer still face acute and chronic toxicities such as fatigue, cardiotoxicity, pain, cognitive impairment, and neurotoxicity. In this narrative review, we briefly discuss the use of exercise for toxicity management in patients with cancer, biological mechanisms underlying the toxicities and the effects of exercise, barriers that patients- especially underserved patients-face in adopting and adhering to exercise programs, and new technologies to overcome barriers to exercise. Our conclusions and clinical suggestions are: (1) exercise is safe and effective for treating many toxicities; (2) patients can benefit from a variety of exercise modalities (e.g., walking, cycling, resistance bands, yoga); (3) exercise should be started as soon as possible, even before treatments begin; (4) exercise should be continued as long as possible, as a lifestyle; and (5) barriers to exercise should be identified and addressed, (e.g., continually encouraging patients to exercise, using mobile technology, advocating for safe communities that encourage active lifestyles). Future research should inform definitive clinical guidelines for the use of exercise to ameliorate toxicities from cancer and its treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922767PMC
February 2018

Exercise for managing cancer- and treatment-related side effects in older adults.

J Geriatr Oncol 2018 07 30;9(4):405-410. Epub 2018 Mar 30.

James P. Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA.

The incidence of cancer in adults aged 60 years and older is expected to rise, and because cancer is associated with aging, the overall prevalence of cancer will rise as well. With advances in cancer treatment, more older adults will receive treatment but they will also suffer the biopsychosocial consequences of cancer and cancer treatment. In this review, we describe the importance of assessing biopsychosocial needs in this vulnerable population and highlight studies supporting the use of exercise in addressing these needs. We discuss challenges and research gaps in several areas including 1) Identifying the exercise doses and modes for specific outcomes, 2) Understanding risks and safety of exercise, and 3) Implementing exercise programs into clinical practice at the individual, health care team, and organizational levels, including strategies to increase adherence.
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http://dx.doi.org/10.1016/j.jgo.2018.03.003DOI Listing
July 2018

Comparison the clinical outcomes with altered versus conventional fractionated radiotherapy plus concurrent chemotherapy for advanced nasopharyngeal carcinoma.

Head Neck 2018 06 1;40(6):1156-1163. Epub 2018 Feb 1.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Background: The purpose of this study was to compare the long-term survivals between altered fractionated and conventional fractionated radiotherapy with the same concurrent chemoradiotherapy (concurrent CRT) for patients with advanced nasopharyngeal carcinoma (NPC).

Methods: We retrospectively reviewed 203 patients with NPC who received radiotherapy (RT) by either a conventional fractionated (70-74 Gy/35-37 fractions/7-8 weeks) or altered fractionated (72-75 Gy/45 fractions/6 weeks) schedule plus the same concurrent CRT.

Results: The patient characteristics between conventional fractionated and altered fractionated groups showed similar distribution. The 5-year rates of nasopharyngeal failure-free, neck failure-free, and distant metastasis failure-free survival between conventional fractionated and altered fractionated groups were 88% versus 86% (P = .7781), 95% versus 93% (P = .4176), and 76% versus 73% (P = .4029), respectively. The overall survival (OS; 5-year rates were 64% versus 62%; P = .4812) and progression-free survival (PFS; 5-year rates were 67% versus 63%; P = .3829) rates also showed no significant differences. The acute and late toxicities were similar between both groups.

Conclusion: Altered fractionated and conventional fractionated RT achieved similar survival outcome when concurrent CRT strategy was used for advanced NPC.
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http://dx.doi.org/10.1002/hed.25084DOI Listing
June 2018

Yoga for the Management of Cancer Treatment-Related Toxicities.

Curr Oncol Rep 2018 02 1;20(1). Epub 2018 Feb 1.

Department of Surgery, James P. Wilmot Cancer Institute, University of Rochester Medical Center, 265 Crittenden Blvd., Box CU 420658, Rochester, NY, 14642, USA.

Purpose Of Review: To (1) explain what yoga is, (2) summarize published literature on the efficacy of yoga for managing cancer treatment-related toxicities, (3) provide clinical recommendations on the use of yoga for oncology professionals, and (4) suggest promising areas for future research.

Recent Findings: Based on a total of 24 phase II and one phase III clinical trials, low-intensity forms of yoga, specifically gentle hatha and restorative, are feasible, safe, and effective for treating sleep disruption, cancer-related fatigue, cognitive impairment, psychosocial distress, and musculoskeletal symptoms in cancer patients receiving chemotherapy and radiation and cancer survivors. Clinicians should consider prescribing yoga for their patients suffering with these toxicities by referring them to qualified yoga professionals. More definitive phase III clinical trials are needed to confirm these findings and to investigate other types, doses, and delivery modes of yoga for treating cancer-related toxicities in patients and survivors.
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http://dx.doi.org/10.1007/s11912-018-0657-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901971PMC
February 2018

Comparison Long-term Outcome of Definitive Radiotherapy plus Different Chemotherapy Schedules in Patients with Advanced Nasopharyngeal Carcinoma.

Sci Rep 2018 01 11;8(1):470. Epub 2018 Jan 11.

Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.

Concurrent chemoradiotherapy (CCRT) is the current standard of care for advanced nasopharyngeal carcinoma (NPC). We hypothesize that shifting CCRT to neoadjuvant chemotherapy followed by radiotherapy (NeoCT-RT) is an alternative option. From December 2004 to January 2009, 256 NPC patients with stage II-IVB were treated by either CCRT or NeoCT-RT. All patients received the same dosage and fractionation schedule of RT. After long-term follow-up, 26.8% (34/127) and 23.3% (30/129) of patients who received CCRT and NeoCT-RT respectively, developed a tumor relapse (P = 0.6134). Overall survival (HR = 1.52, 95%CI = 0.91-2.55, P = 0.1532) and progression-free survival (HR = 1.22, 95%CI = 0.75-1.99, P = 0.4215) were similar in both groups. However, acute toxicities during RT period revealed a significant reduction of grade 3/4 vomiting (23% vs. 0%, P < 0.0001), mucositis (55% vs. 16%, P < 0.0001), and neck dermatitis (31% vs. 16%, P = 0.0041) in the NeoCT-RT group, resulting in fewer emergency room visits (10.2% vs. 1.6%, P = 0.0071). Severe treatment-related late toxicity (15% vs. 14%, P = 0.9590) and the occurrence of second malignancy (3.9% vs. 5.4%, P = 0.7887) also showed no differences. We concluded that NeoCT-RT could be an attractive alternative option of CCRT for advanced NPC.
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http://dx.doi.org/10.1038/s41598-017-18713-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764995PMC
January 2018

Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial.

Support Care Cancer 2018 Apr 14;26(4):1019-1028. Epub 2017 Dec 14.

James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.

Purpose: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms.

Methods: Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness.

Results: Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076).

Conclusions: Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients.

Trial Registration: Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .
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http://dx.doi.org/10.1007/s00520-017-4013-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823751PMC
April 2018

Low-Carbohydrate-High-Fat Diet: Can it Help Exercise Performance?

J Hum Kinet 2017 Feb 12;56:81-92. Epub 2017 Mar 12.

School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.

Low-carbohydrate-high-fat (LCHF) diets have been used as a means of weight loss and control of symptoms in several clinical conditions. There is emerging evidence that the metabolic changes induced by LCHF diets enhance endurance performance. The aims of this review are to examine the evidence of LCHF diets in improving various aspects of athletic performance. Long-term LCHF dietary intake may help control body weight and fat mass while maintaining lean body mass in athletes in weight-sensitive sports. LCHF-adapted endurance athletes can reach the maximal fat oxidation rate of approximately 1.5 g/min, with a lower carbohydrate oxidation rate and similar muscle glycogen content and a resynthesis rate compared to their counterparts consuming high-carbohydrate-low-fat (HCLF) diets. The elevated fat oxidation rate and glycogen sparing effect may improve performance in ultra-endurance events. These metabolic changes may also prevent the decline in performance in later stages of repeated high-intensity movements, in which the aerobic metabolism becomes more important. However, elevated blood concentrations of non-esterified fatty acids and ammonia during exercise after LCHF diets may lead to early development of central fatigue. It appears that at least several months of adaptation to a LCHF diet are required for the metabolic changes and restoration of muscle glycogen to occur. Further investigations on LCHF diets are needed regarding (1) performance after weight loss in weight-categorized sports; (2) repeated high-intensity exercise performance; (3) development of central fatigue during endurance events; (4) perceptual-motor performance during prolonged intermittent sports; and (5) ideal dietary fatty acid compositions.
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http://dx.doi.org/10.1515/hukin-2017-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384055PMC
February 2017

Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients.

Oral Oncol 2017 01 30;64:15-21. Epub 2016 Nov 30.

Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Objectives: To investigate the prognostic impact of adjuvant chemotherapy (AdjCT) in patients with high-risk nasopharyngeal carcinoma (NPC).

Materials And Methods: A total 403 NPC patients with at least one of the following criteria (1) neck node>6cm; (2) supraclavicular node metastasis; (3) skull base destruction/intracranial invasion plus multiple nodes metastasis; or (4) multiple neck nodes metastasis with one of nodal size>4cm were retrospectively reviewed. All patients finished curative radiotherapy±neoadjuvant/concurrent chemotherapy. Post-radiation AdjCT consisted of tegafur-uracil (two capsules twice daily) for 12months. We analyzed the treatment outcome between patients with (n=154) and without (n=249) AdjCT.

Results: Baseline patient characteristics at diagnosis (age, gender, pathological type, performance status, T-classification, N-classification, and overall stage) were comparable in both arms. After a median follow-up of 72months for surviving patients, 31.8% (49/154) and 42.2% (105/249) in patients with and without AdjCT developed tumor relapse respectively (P=0.0377). AdjCT improved both overall survival (HR 1.89, 95% CI 1.37-2.61, P=0.0001) and progression-free survival (HR 1.42, 95% CI 1.03-1.96, P=0.0322). There were significant reduction in distant failures (P=0.0016) but not in local (P=0.8587) or regional (P=0.8997) recurrences for patients who received AdjCT.

Conclusion: AdjCT can reduce distant failure and improve overall survival in high-risk NPC patients after curative radiotherapy±neoadjuvant/concurrent chemotherapy.
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http://dx.doi.org/10.1016/j.oraloncology.2016.11.008DOI Listing
January 2017

Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration.

EMBO Mol Med 2017 02;9(2):251-264

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regulation of several mitosis-related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3-shRNA (FIJs), induced CMs to re-enter the cell cycle and complete mitosis and cytokinesis in vitro More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction. Collectively, our findings present a cocktail FIJs that may be useful in cardiac regeneration and also provide a practical strategy for probing reprogramming assays for regeneration of other tissues.
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http://dx.doi.org/10.15252/emmm.201606558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286362PMC
February 2017

Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance.

PLoS One 2016 31;11(10):e0165378. Epub 2016 Oct 31.

School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.

Background: Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states.

Methods: Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR).

Results: The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia.

Conclusions: Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to 30% compared to no such changes after three 60%-carbohydrate meals, an effect that was independent of pre-meal exercise. The parallel timing and magnitude of postprandial insulin and GIP changes suggest their dependence on a delayed intestinal adaptation to a low-carbohydrate diet. Pre-meal exercise exacerbated glucose intolerance with both diets most likely due to impairment of insulin signaling by pre-meal elevation of FFAs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165378PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087910PMC
June 2017

Exercise Recommendations for the Management of Symptoms Clusters Resulting From Cancer and Cancer Treatments.

Semin Oncol Nurs 2016 11 21;32(4):383-393. Epub 2016 Oct 21.

Objective: To review existing exercise guidelines for cancer patients and survivors for the management of symptom clusters.

Data Sources: Review of PubMed literature and published exercise guidelines.

Conclusion: Cancer and its treatments are responsible for a copious number of incapacitating symptoms that markedly impair quality of life. The exercise oncology literature provides consistent support for the safety and efficacy of exercise interventions in managing cancer- and treatment-related symptoms, as well as improving quality of life in cancer patients and survivors.

Implications For Nursing Practice: Effective management of symptoms enhances recovery, resumption of normal life activities and quality of life for patients and survivors. Exercise is a safe, appropriate, and effective therapeutic option before, during, and after the completion of treatment for alleviating symptoms and symptom clusters.
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http://dx.doi.org/10.1016/j.soncn.2016.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512003PMC
November 2016

Long-term clinical outcome in nasopharyngeal carcinoma patients with post-radiation persistently detectable plasma EBV DNA.

Oncotarget 2016 Jul;7(27):42608-42616

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Purpose: To investigate the long-term clinical outcome of nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma EBV (pEBV) DNA after curative radiotherapy (RT).

Results: The post-RT pEBV DNA levels were very lower copy number (median 21, interquartile range 8-206 copies/ml). After long-term follow-up, the relapse rate was 64.8%, the median time to progression 20 months, and 5-year overall survival (OS) 49.6%. Thirty-two of 39 (82.1%) patients with high viral load (≥ 100 copies/ ml) developed tumor relapse, whereas 57.0% (49/86) patients with low viral load (< 100 copies/ml) had tumor relapse (P = 0.0065). The 5-year OS rates were 20.5% and 62.9% for patients with viral load ≥ and < 100 copies/ml (median survival, 20 vs. 100 months; P < 0.0001). Patients who received adjuvant chemotherapy (AdjCT) experienced significant reduction in distant failures (66.2% vs. 31.6%; P = 0.0001) but similar locoregional recurrences (P = 0.2337). The 5-year OS rates were 69.4% for patients who received AdjCT compared with 33.2% for those of without AdjCT (median survival, 111 vs. 32 months; P < 0.0001).

Methods: We screened 931 newly diagnosed NPC patients who finished curative RT and found 125 patients (13.4%) with detectable pEBV DNA one week after RT. The clinical characteristics, treatment modality, subsequent failure patterns and survivals were analyzed.

Conclusions: NPC patients with persistently detectable pEBV DNA after curative RT have a higher rate of treatment failure and poor survivals. Levels of the post-RT pEBV DNA and administration of AdjCT affect the final outcome significantly.
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http://dx.doi.org/10.18632/oncotarget.9323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173160PMC
July 2016
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