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1.  A Peptide-based, Two-fluorophore, Ratiometric Probe for Quantifying Mobile Zinc in Biological Solutions 
ACS chemical biology  2014;10(2):385-389.
Small-molecule fluorescent sensors are versatile agents for detecting mobile zinc in biology. Capitalizing on the abundance of validated mobile zinc probes, we devised a strategy for repurposing existing intensity-based sensors for quantitative applications. Using solid-phase peptide synthesis, we conjugated a zinc-sensitive Zinpyr-1 derivative and a zinc-insensitive 7-hydroxycoumarin derivative onto opposite ends of a rigid P9K peptide scaffold to create HcZ9, a ratiometric fluorescent probe for mobile zinc. A plate reader-based assay using HcZ9 was developed, the accuracy of which is comparable to that of flameless atomic absorption spectroscopy. We investigated zinc accumulation in prostatic cells and zinc levels in human seminal fluid. When normal and tumorigenic cells are bathed in zinc-enriched media, cellular mobile zinc is buffered and changes slightly, but total zinc levels increase significantly. Quantification of mobile and total zinc levels in human seminal plasma revealed that the two are positively correlated with a Pearson’s coefficient of 0.73.
doi:10.1021/cb500617c
PMCID: PMC4336589  PMID: 25382858
2.  Weight and weight change following breast cancer: evidence from a prospective, population-based, breast cancer cohort study 
BMC Cancer  2015;15:28.
Background
While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics.
Methods
A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight.
Results
More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9 kg [2.0-11.3 kg] and 5.2 kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: −6.4 kg [−1.9--24.6 kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3 kg; all p < 0.05).
Conclusions
While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.
doi:10.1186/s12885-015-1026-2
PMCID: PMC4318545  PMID: 25637285
Breast cancer; Body weight; Longitudinal cohort study; Public health
3.  Health Related Quality of Life, Lifestyle Behaviors, and Intervention Preferences of Survivors of Childhood Cancer 
Journal of cancer survivorship : research and practice  2013;7(4):10.1007/s11764-013-0289-3.
PURPOSE
Childhood cancer survivors (CCSs) are at increased risk for poor health-related quality of life (HRQOL) and chronic health conditions -- both of which can be exacerbated by unhealthy lifestyle behaviors. Developing a clearer understanding of the associations between HRQOL, lifestyle behaviors, and medical and demographic variables (e.g., age/developmental stage at time of diagnosis) is an important step toward developing more targeted behavioral interventions for this population.
METHOD
Cross-sectional questionnaires were completed by 170 CCSs who were diagnosed with leukemia, lymphoma, sarcoma, or a cancer of the central nervous system (CNS) and treated at a comprehensive cancer center between 1992 and 2007. Questionnaires addressed weight status, lifestyle behaviors, aspects of HRQOL, and intervention preferences.
RESULTS
Adolescent and young adult survivors (AYAs) and survivors of CNS tumors or lymphoma reported significantly (p<.05) poorer HRQOL across multiple domains compared to those diagnosed at an earlier age, survivors of leukemia or sarcoma, and healthy populations. A significant proportion also failed to meet national recommendations for dietary intakes (39–94%) and physical activity (65%). Female survivors reported poorer physical functioning and consumed less dietary fiber and fruits and vegetables than did male survivors. They also expressed the strongest interest in participating in diet and exercise interventions.
CONCLUSION
Findings support the premise that females, AYAs, and survivors of cancers of the CNS or lymphoma are “at risk” subgroups within the CCS population for poor dietary practices, sedentary behaviors, and poor HRQOL. Future research should focus on developing diet and PA interventions to improve HRQOL that target these groups.
IMPLICATIONS FOR SURVIVORS
Greater consideration of the role of gender, developmental stage, and the HRQOL challenges facing CCSs may help researchers to develop targeted behavioral interventions for those who stand to benefit the most.
doi:10.1007/s11764-013-0289-3
PMCID: PMC3825822  PMID: 23749663
childhood cancer; diet; physical activity; health related quality of life; intervention preferences
4.  Identifying Early Dehydration Risk With Home-Based Sensors During Radiation Treatment: A Feasibility Study on Patients With Head and Neck Cancer 
Background
Systems that enable remote monitoring of patients’ symptoms and other health-related outcomes may optimize cancer care outside of the clinic setting. CYCORE (CYberinfrastructure for COmparative effectiveness REsearch) is a software-based prototype for a user-friendly cyberinfrastructure supporting the comprehensive collection and analyses of data from multiple domains using a suite of home-based and mobile sensors. This study evaluated the feasibility of using CYCORE to address early at-home identification of dehydration risk in head and neck cancer patients undergoing radiation therapy.
Methods
Head and neck cancer patients used home-based sensors to capture weight, blood pressure, pulse, and patient-reported outcomes for two 5-day periods during radiation therapy. Data were sent to the radiation oncologist of each head and neck cancer patient, who viewed them online via a Web-based interface. Feasibility outcomes included study completion rate, acceptability and perceived usefulness of the intervention, and adherence to the monitoring protocol. We also evaluated whether sensor data could identify dehydration-related events.
Results
Fifty patients consented to participate, and 48 (96%) completed the study. More than 90% of patients rated their ease, self-efficacy, and satisfaction regarding use of the sensor suite as extremely favorable, with minimal concerns expressed regarding data privacy issues. Patients highly valued the ability to have immediate access to objective, self-monitoring data related to personal risk for dehydration. Clinician assessments indicated a high degree of satisfaction with the ease of using the CYCORE system and the resulting ability to monitor their patients remotely.
Conclusion
Implementing CYCORE in a clinical oncology care setting is feasible and highly acceptable to both patients and providers.
doi:10.1093/jncimonographs/lgt016
PMCID: PMC3881993  PMID: 24395986
5.  A Comparison of Cancer Survivors from the PROMIS Study Selecting Telephone Versus Online Questionnaires 
Psycho-oncology  2013;22(11):10.1002/pon.3330.
doi:10.1002/pon.3330
PMCID: PMC3808510  PMID: 23813785
cancer; oncology; data collection; surveys; internet; telephone
6.  Weight gain prior to entry into a weight-loss intervention study among overweight and obese breast cancer survivors 
Purpose
Changes in cancer therapy, in addition to changes in obesity prevalence, suggest the need for a current assessment of weight gain patterns following breast cancer diagnosis. The aim of this study was to evaluate factors associated with weight gain among breast cancer survivors prior to enrolling into a behavioral weight loss intervention.
Methods
Anthropometric measures and data on weight-related factors were collected at baseline on 665 breast cancer survivors. Postdiagnosis weight gain was determined between entry into the trial and previous diagnosis up to 5 years. Multivariate logistic regression analyses were used to evaluate the association between weight gain and influencing factors.
Results
The mean weight gain was 4.5 % body weight (standard deviation=10.6); 44 % of women experienced ≥5 % body weight gain. The risk of weight gain was inversely associated with age (adjusted odds ratio (ORadj)=0.97, 95 % confidence interval (95 % CI) 0.95–0.99), Hispanic ethnicity (ORadj=0.30, 95 % CI 0.13–0.68), and overweight (ORadj= 0.11, 95 % CI 0.05–0.23) or obese (ORadj=0.03, 95 % CI 0.02–0.07) status at diagnosis and positively associated with time elapsed since diagnosis (ORadj=1.19/year, 95 % CI 1.04–1.36). Women prescribed aromatase inhibitors were 46 % less likely to gain weight compared to women prescribed selective estrogen-receptor modulators (ORadj=0.54, 95 % CI 0.31–0.93). The risk of weight gain was positively associated with smoking at diagnosis (ORadj=2.69, 95 % CI 1.12–6.49) although this was attributable to women who subsequently quit smoking.
Conclusions
Postdiagnosis weight gain is common and complex and influenced by age, ethnicity, weight, smoking status, time elapsed since diagnosis, and endocrine-modulating therapy.
Implications for cancer survivors
Weight gain continues to be a concern following a diagnosis of breast cancer. Factors influencing this weight gain include age, ethnicity, weight, smoking status, time elapsed since diagnosis, and endocrine-modulating therapy. Effective weight management strategies are needed for this population of women.
doi:10.1007/s11764-014-0351-9
PMCID: PMC4127359  PMID: 24599421
Breast cancer survivors; Weight gain; Women
7.  Diet, physical activity, and body composition changes during the first year of treatment for childhood acute leukemia and lymphoma 
Background
Children who undergo treatment for childhood acute lymphoblastic leukemia (ALL) and lymphoma are at risk for several long-term health problems. Obesity, for which survivors of ALL and lymphoma are also at risk, may further exacerbate these problems. This pilot study evaluates changes in physical activity and body composition among children being treated for ALL and lymphoma and their parents.
Procedures
Recently diagnosed adolescent ALL and lymphoma patients were recruited from two pediatric hematology and oncology clinics, and matched on age, race, and gender to healthy individuals in the community. Changes in diet, physical activity and body composition were collected at baseline, 6, and 12 months.
Results
All children (n = 15) were, on average, 10.3 years of age at enrollment, and were fairly evenly distributed with regard to gender. Analyses revealed a significant difference between cases and controls with respect to the change in BMI from baseline to 12 months (p = 0.01). Additionally, controls demonstrated a significantly greater increase in moderate-vigorous physical activity (MVPA) than the cases (229.8 Metabolic equivalent of tasks [METs] vs. 23.5 METs); indicating cases remained fairly inactive over the course of treatment.
Conclusion
Our data corroborate previous findings that, following treatment for ALL and lymphoma, childhood cancer survivors tend to be less active and at greater risk for obesity than their healthy peers. The present study, which assessed cases prospectively over a 12 month period during the early phases of treatment, extends prior reports by demonstrating that these outcomes are evident at an early stage in treatment.
doi:10.1097/MPH.0b013e318279cd3e
PMCID: PMC3606649  PMID: 23211695
childhood acute lymphoblastic leukemia and lymphoma; obesity; physical activity; diet
8.  Cognitive Influences as Mediators of Family and Peer Support for Pediatric Cancer Survivors’ Physical Activity 
Psycho-oncology  2012;22(6):1361-1368.
Objective
Determine the extent to which self-efficacy mediates the relations between social support and childhood cancer survivors’ physical activity (PA).
Methods
A structured telephone survey was conducted with 105 childhood cancer survivor ages 8–16. Participants completed measures assessing their physical activity as well as proposed predictors of PA including various demographic, medical, cognitive, and social influences. Multiple mediation analyses were utilized to evaluate the relations between social support, cognitive influences, and survivor PA.
Results
Cognitive influences, including perceived benefits, barriers, and self-efficacy for PA, partially mediated the influence of family and peer support on survivor PA. Self-efficacy emerged as a significant unique mediator, indicating that higher levels of family and peer support are associated with higher levels of survivor PA via increases in survivor self-efficacy.
Conclusions
Social support has both direct and indirect influences on survivor PA. Indirectly, social support influences PA via survivor self-efficacy. Interventions should target family and peer support as well as self-efficacy to increase survivor PA.
doi:10.1002/pon.3140
PMCID: PMC3511656  PMID: 22826210
Cancer; childhood; physical activity; survivors; mediation
9.  Cancer-Specific Concerns and Physical Activity Among Recently Diagnosed Breast and Prostate Cancer Survivors 
Integrative cancer therapies  2012;12(3):206-212.
Background
Cancer treatment-related side effects may have a negative impact on quality of life among cancer survivors, and may limit participation in physical activity.
Hypothesis
Cancer-specific concerns will be reduced throughout a 10-month diet and exercise intervention among recently-diagnosed cancer survivors. Additionally, participants reporting greater levels of physical activity will also report fewer cancer-specific concerns.
Study Design
This study is an exploratory analysis of 452 recently diagnosed, early stage breast and prostate cancer survivors who participated in the FRESH START diet and exercise trial. Data were collected at baseline and 1-year follow-up via telephone administration of the Functional Assessment of Cancer Therapy (FACT) instrument and the 7-Day Physical Activity Recall.
Results
At baseline, chief concerns among prostate cancer survivors included ability to have an erection (mean score [SD]: 1.0 [1.3]) and urinary frequency (2.5 [1.4]), whereas among breast cancer survivors eminent concerns were not feeling sexually attractive (2.0 [1.3]) and worry about cancer in other members of their family (2.1 [1.3]). At 1 year, there was a significant improvement in cancer-specific concerns on breast cancer specific-concerns (p<0.01), but not on prostate cancer-specific concerns. Physical activity (PA) was generally not related to cancer-specific concerns, though at baseline women who were self-conscious about their dress had higher levels of PA, whereas men reporting issues with incontinence reported lesser increases in PA in response to the intervention.
Conclusion
While cancer survivors have several cancer-specific concerns, these concerns diminish over time, especially among breast cancer survivors. Furthermore, this reduction appears independent of changes in physical activity. Among prostate cancer survivors, incontinence is a significant barrier that hinders benefit from PA interventions. Thus, there is a need either for medical interventions to ameliorate incontinence or for behavioral interventions to address this issue among survivors, especially given the importance of PA for overall health.
doi:10.1177/1534735412449734
PMCID: PMC3764991  PMID: 22879576
breast neoplasms; prostatic neoplasms; physical activity; quality of life
10.  Androgenetic Alopecia at Various Ages and Prostate Cancer Risk in an Equal Access Multiethnic Case Control Series of Veterans 
Cancer causes & control : CCC  2013;24(5):1045-1052.
Purpose
Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions.
Materials and Methods
We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30, 40 and at study enrollment. We tested the association between hair pattern (overall, vertex or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome.
Results
Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p=0.008). Similar patterns were noted for frontal (p=0.005) and not vertex balding (p=0.22). When compared to biopsy negative men, a similar pattern was seen with younger age of AA onset having higher risk for CaP, though this was not significant (p=0.07). A suggestion for younger age of AA onset for frontal (p=0.07) being associated with CaP vs. biopsy negative men was also observed. Overall balding (yes/no) was associated with > 2-fold increase of high-grade disease (p=0.02).
Conclusions
Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.
doi:10.1007/s10552-013-0182-4
PMCID: PMC3640447  PMID: 23529469
11.  Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods 
BMC Cancer  2014;14:238.
Background
Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments.
Methods/Design
This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation.
Discussion
This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform intervention programs that will optimally improve physiological and psychosocial health during cancer survivorship, and that are ultimately aimed at improving prognosis.
Trial registration
NCT01140282; Registration: June 10, 2010
doi:10.1186/1471-2407-14-238
PMCID: PMC3985576  PMID: 24708832
Exercise; Breast cancer; Metabolic syndrome
12.  Long-term Outcomes of the FRESH START Trial: Exploring the Role of Self-efficacy in Cancer Survivors’ Maintenance of Dietary Practices and Physical Activity 
Psycho-oncology  2012;22(4):876-885.
Objective
This study examined whether changes in self-efficacy explain the effects of a mailed print intervention on long-term dietary practices of breast and prostate cancer survivors. The relationship between change in self-efficacy and long-term physical activity (PA) also was examined.
Methods
Breast and prostate cancer survivors (N=543) from 39 U.S. states and two Canadian provinces participated in the FRESH START intervention trial. Participants were randomly assigned to receive a 10-month program of mailed print materials on diet and PA available in the public domain or a 10-month program of tailored materials designed to increase fruit and vegetable (F&V) intake, decrease fat intake, and/or increase PA. Changes in self-efficacy for F&V intake and fat restriction were analyzed as potential mediators of the intervention’s effects on diet at 2-year follow-up. Because we previously found that change in self-efficacy for PA did not vary by group assignment, the relationship between change in self-efficacy and PA at 2-year follow-up was examined across study conditions.
Results
Results suggest that change in self-efficacy for fat restriction partially explained the intervention’s effect on fat intake (mean indirect effect=-.28), and change in self-efficacy for F&V consumption partially explained the intervention’s effect on daily F&V intake (mean indirect effect=.11). Change in self-efficacy for fat restriction partially accounted for the intervention’s impact on overall diet quality among men only (mean indirect effect=.60). Finally, change in self-efficacy for PA predicted PA at 2-year follow-up.
Conclusions
Findings suggest that self-efficacy may influence long-term maintenance of healthy lifestyle practices among cancer survivors.
doi:10.1002/pon.3089
PMCID: PMC3429767  PMID: 22544562
cancer; oncology; survivors; diet; physical activity; randomized controlled trial
13.  Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer 
Journal of Medicinal Food  2013;16(4):357-360.
Abstract
Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NFκB) and vascular endothelial growth factor (VEGF). We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NFκB, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for ∼30 days. Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively. After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (ρ=0.677, P<.0001), enterolactone (ρ=0.676, P<.0001), and enterodiol (ρ=0.628, P<.0001). Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (ρ=−0.217, P=.011, and ρ=−0.230, P=.007, respectively), and a near-significant inverse association was observed for enterodiol (ρ=−0.159, P=.064). An inverse association was observed between enterolactone and VEGF (ρ=−0.143, P=.141), although this did not reach statistical significance. We did not observe an association between enterolignans and NFκB. In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.
doi:10.1089/jmf.2012.0159
PMCID: PMC3624628  PMID: 23566060
diet; flaxseed; lignans; phytoestrogens; prostatic neoplasia
14.  Carbohydrate Restriction, Prostate Cancer Growth, and the Insulin-Like Growth Factor Axis 
The Prostate  2008;68(1):11-19.
BACKGROUND
Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model.
METHODS
Seventy-five male SCID mice were fed a NCKD (84% fat–0% carbohydrate–16% protein kcal), low-fat (12% fat–72% carbohydrate–16% protein kcal), or Western diet (40% fat–44% carbohydrate–16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm3.
RESULTS
Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P = 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms.
CONCLUSIONS
In this xenograft model, despite consuming more calories, NCKD-fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet.
doi:10.1002/pros.20683
PMCID: PMC3959866  PMID: 17999389
prostatic neoplasms; diet; carbohydrate; fat; ketogenesis; insulin; IGF-1
15.  Obesity is associated with higher 4E-BP1 expression in endometrial cancer 
Current biomarker findings  2014;2014(4):1-7.
Purpose
Obesity is associated with risk and prognosis of endometrial cancer (EC), and the mammalian target of rapamycin complex 1 (mTORC1) pathway may play an instrumental role. We sought to explore the associations between cellular proliferation, Akt, and 4E binding protein-1 (4E-BP1) (a downstream target of mTORC1), in obese and nonobese women with and without EC.
Methods
Archival tissue-specimens from endometrial biopsies were grouped into two broad categories based on the observed disease behavior and similarities in tissue staining patterns: benign/hyperplasia (without cytologic atypia) (n=18) versus atypia (complex hyperplasia with cytologic atypia)/carcinoma (n=25). The characteristics of the study population, including height and weight to determine body mass index (BMI: kg/m2), were abstracted from medical records. Immunohistochemistry was used to assess the phosphorylated (p)Akt, p4E-BP1, and antigen Ki67.
Results
Cytoplasmic and nuclear pAkt were significantly associated with cytoplasmic p4E-BP1 (ρ=+0.48, ρ=+0.50) (P<0.05) and nuclear p4E-BP1 (ρ=+0.40, ρ=+0.44) (P<0.05); cytoplasmic and nuclear p4E-BP1 were significantly associated with Ki67 (ρ=+0.46, ρ=+0.59) (P<0.05). Compared with the benign/hyperplasia group, the women with atypia/carcinoma had significantly higher cytoplasmic and nuclear p4E-BP1 and Ki67. This staining pattern was similar in obese women; however, in nonobese women, neither cytoplasmic nor nuclear p4E-BP1staining differed between benign/hyperplasia versus atypia/carcinoma.
Conclusion
The activation of 4E-BP1 was higher in the obese women with EC. Adiposity may be a key factor to consider in future studies investigating the role of 4E-BP1 as a biomarker and therapeutic target in EC.
doi:10.2147/CBF.S53530
PMCID: PMC3955094  PMID: 24639918
mTORC1; immunohistochemistry; gynecologic malignancy; corpus uterine; BMI; biomarker
16.  Reducing Breast Cancer Recurrence with Weight Loss, a Vanguard Trial: The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial 
Contemporary clinical trials  2012;34(2):282-295.
Breast cancer is the most common invasive cancer among women in developed countries. Obesity is a major risk factor for breast cancer recurrence and mortality in both pre-and postmenopausal women. Co-morbid medical conditions are common among breast cancer survivors. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is a 4-year randomized clinical trial of 693 overweight/obese women aged ≥21 years diagnosed with any early stage breast cancer (stages I[≥1 cm]-III) within the previous five years, designed to demonstrate the feasibility of achieving sustained weight loss and to examine the impact of weight loss on quality of life and co-morbidities, and to enable future exploration of biochemical mechanisms linking obesity to lower likelihood of disease-free survival. This trial is strategically designed as a vanguard for a fully-powered trial of women who will be evaluated for breast cancer recurrence and disease-free survival. Participants were recruited between 2010 and 2012 at four sites, had completed initial therapies, and had a body mass index between 25 and 45 kg/m2. The intervention featured a group-based cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance, with the goal of 7% weight loss at two years. This study has high potential to have a major impact on clinical management and outcomes after a breast cancer diagnosis. This trial initiates the effort to establish weight loss support for overweight or obese breast cancer survivors as a new standard of clinical care.
doi:10.1016/j.cct.2012.12.003
PMCID: PMC3593786  PMID: 23266440
Obesity; Weight Reduction; Breast Cancer; Quality of Life; Co-Morbidities
17.  Differences in Baseline Characteristics and Outcomes at One-and Two-Year Follow-up of Cancer Survivors Accrued via Self-Referral versus Cancer Registry in the FRESH START Diet and Exercise Trial 
Participant accrual to research studies is a challenge, and oftentimes advertisements are used to supplement cases ascertained through clinic caseloads and cancer registries. It is unknown however, if cases ascertained through these two sources differ. In this study, we compare self-referred (n=209) versus cancer registry-ascertained participants (n=334) enrolled in FRESH START, a randomized controlled trial promoting a healthy diet and increased exercise among breast and prostate cancer survivors. The two groups were compared on baseline characteristics, adherence, attrition, and outcomes by study arm. Compared to participants enrolled from registries, self-referrals were significantly younger (54.1±10.4 vs. 58.7±10.7 years), more likely to have later-staged disease and to have received chemotherapy (40% vs. 19%), and more likely to report “fighting spirit” coping styles (50% vs. 30%), lower quality-of-life (88.2+15.1 vs. 92.0+12.9), fewer co-morbid conditions (1.87±1.60 vs. 2.24±1.78), and lower consumption of 5 or more daily servings of fruits and vegetables (35% vs. 45%)(p-values <.05). While no differences in behavior change were observed between self-referred and registry-ascertained cases assigned to the tailored intervention arm, this was not the case within the attention control arm. Among those who received the attention control intervention of standardized materials in the public domain, self-referred versus registry-ascertained participants demonstrated significantly greater increases in exercise at 1-year follow-up, and significantly greater increases in fruit and vegetable consumption at both 1- and 2-year follow-up (p-values <.05). Several differences exist between self-referred versus registry-ascertained participants, including motivation to respond to standardized educational materials which appears significantly greater in self-referred populations.
doi:10.1158/1055-9965.EPI-07-0705
PMCID: PMC3842166  PMID: 18483353
patient selection; registries; neoplasms; advertising
18.  Developing an intervention to address physical activity barriers for African–American women in the deep south (USA) 
Women's health (London, England)  2013;9(3):10.2217/whe.13.20.
Aim
To address high rates of inactivity and related chronic diseases among African–American women.
Materials & methods
Eleven focus groups on physical activity barriers for African–American women in the deep south (USA) were conducted (n = 56). Feedback guided an intervention development process. The resulting Home-Based Individually Tailored Physical Activity Print intervention was vetted with the target population in a 1-month, single arm, pre–post test demonstration trial (n = 10).
Results
Retention was high (90%). Intent-to-treat analyses indicated increases in motivational readiness for physical activity (70% of sample) and physical activity (7-day Physical Activity Recall) from baseline (mean: 89.5 min/week, standard deviation: 61.17) to 1 month (mean: 155 min/week, standard deviation: 100.86). Small improvements in fitness (6-Min Walk Test), weight and psychosocial process measures were also found.
Conclusion
Preliminary findings show promise and call for future randomized controlled trials with larger samples to determine efficacy. Such low-cost, high-reach approaches to promoting physical activity have great potential for addressing health disparities and benefiting public health.
doi:10.2217/whe.13.20
PMCID: PMC3816507  PMID: 23638785
African–merican women; exercise; health disparity; physical activity
19.  Obesity, Energy Balance and Cancer: New Opportunities for Prevention 
Obesity is associated with increased risk and poor prognosis for many types of cancer. The mechanisms underlying the obesity-cancer link are becoming increasingly clear and provide multiple opportunities for primary to tertiary prevention. Several obesity-related host factors can influence tumor initiation, progression and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. These host factors include insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, cytokines, and inflammation-related molecules. Each of these host factors is considered in the context of energy balance and as potential targets for cancer prevention. The possibility of prevention at the systems level, including energy restriction, dietary composition and exercise is considered as is the importance of the newly-emerging field of stem cell research as a model for studying energy balance and cancer prevention.
doi:10.1158/1940-6207.CAPR-12-0140
PMCID: PMC3641761  PMID: 23034147
neoplasms; obesity; diet; growth factors; hormones
20.  Weight Management and its Role in Breast Cancer Rehabilitation 
Cancer  2012;118(8 0):10.1002/cncr.27466.
Overweight and obesity are risk factors for post-menopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery since obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent co-morbid conditions (e.g. cardiovascular disease and diabetes), poorer surgical outcomes (e.g., increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and comorbidity, and improving lifestyle behaviors, functional status, and quality of life in this high-risk patient population.
doi:10.1002/cncr.27466
PMCID: PMC3812811  PMID: 22488702
Breast neoplasms; obesity; weight loss; diet; exercise
21.  LONG-TERM PHYSICAL ACTIVITY OUTCOMES OF HOME-BASED LIFESTYLE INTERVENTIONS AMONG BREAST AND PROSTATE CANCER SURVIVORS 
Purpose
Few studies have investigated long-term effects of physical activity (PA) interventions. The goal of this study was to evaluate whether or not increased levels of moderate to vigorous physical activity (MVPA) were maintained by cancer survivors one-year after receipt of two home-based interventions.
Methods
The FRESH START trial randomized 543 breast and prostate cancer survivors to 1-of-2 mailed print diet and exercise interventions: sequentially-tailored vs. standardized (attention control). Each arm received eight mailings over a 1-year period, with follow-up at 1- and 2-years. This analysis focuses solely on the 400 participants who had suboptimal levels of MVPA at baseline (measured by the 7-Day Physical Activity Recall) and who completed the 2-year study.
Results
Median minutes of MVPA at baseline, 1-year and 2-year follow-up in the tailored intervention arm were as follows: 0, 90, and 60 mins/wk, respectively. The corresponding values in the attention-control group were 0, 30, and 30 mins/wk. Significant improvements in MVPA from baseline to 2-year follow-up were observed in both study arms (p < 0.01). While significant between-arm differences were observed at 1-year follow-up (p < 0.01), by 2-year follow-up there was only the suggestion of a trend (p = 0.08).
Conclusions
This study provides evidence that mailed-print exercise interventions result in significant and sustainable improvements in MVPA among newly-diagnosed cancer survivors that are observed well after the intervention is complete. While tailored interventions, as compared to standardized materials, appear to produce superior improvements in MVPA initially, these differences diminish over time.
doi:10.1007/s00520-011-1370-y
PMCID: PMC3641190  PMID: 22249915
breast neoplasms; prostatic neoplasms; maintenance; physical activity; intervention; durability; exercise
22.  The Effects of Varying Dietary Carbohydrate and Fat Content on Survival in a Murine LNCaP Prostate Cancer Xenograft Model 
Purpose
Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I (IGF-I), both potent prostate cancer mitogens. We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diets, would slow tumor growth and reduce serum insulin, IGF-I, and other molecular mediators of prostate cancer in a xenograft model.
Experimental Design
Individually caged male severe combined immunodeficient mice (n = 130) were randomly assigned to one of three diets (described as percent total calories): very high-fat/no-carbohydrate ketogenic diet (NCKD: 83% fat, 0% carbohydrate, 17% protein), low-fat/high-carbohydrate diet (LFD: 12% fat, 71% carbohydrate, 17% protein), or high-fat/moderate-carbohydrate diet (MCD: 40% fat, 43% carbohydrate, 17% protein). Mice were fed to maintain similar average body weights among groups. Following a preliminary feeding period, mice were injected with 1 × 106 LNCaP cells (day 0) and sacrificed when tumors were ≥1,000 mm3.
Results
Two days before tumor injection, median NCKD body weight was 2.4 g (10%) and 2.1 g (8%) greater than the LFD and MCD groups, respectively (P < 0.0001). Diet was significantly associated with overall survival (log-rank P = 0.004). Relative to MCD, survival was significantly prolonged for the LFD (hazard ratio, 0.49; 95% confidence interval, 0.29–0.79; P = 0.004) and NCKD groups (hazard ratio, 0.59; 95% confidence interval, 0.37–0.93; P = 0.02). Median serum insulin, IGF-I, IGF-I/IGF binding protein-1 ratio, and IGF-I/IGF binding protein-3 ratio were significantly reduced in NCKD relative to MCD mice. Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis, inflammation, insulin resistance, and obesity were also significantly reduced in NCKD relative to MCD tumors.
Conclusions
These results support further preclinical exploration of carbohydrate restriction in prostate cancer and possibly warrant pilot or feasibility testing in humans.
doi:10.1158/1940-6207.CAPR-08-0188
PMCID: PMC3774034  PMID: 19470786
23.  Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis  
International Journal of Oncology  2013;43(4): 1002 - 1010 .
High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggressive) prostate cancer cell lines were characterized, and we explored whether the ApoE variants were associated with tumor aggressiveness generated by intra cellular cholesterol imbalance, using the expression of caveolin-1 (cav-1), a pro-malignancy surrogate of cholesterol overload. Restriction isotyping of ApoE isoforms revealed that the non-aggressive cell lines carried ApoE ε3/ε3 or ε3/ε4 alleles, while the aggressive cell lines carried the Apoε2/ε4 alleles. Our data suggest a contrast between the non-aggressive and the aggressive prostate cancer cell lines in the pattern of cholesterol efflux and cav-1 expression. Our exploratory results suggest a relationship between prostate aggressiveness, ApoE isoforms and cholesterol imbalance. Further investigation of this relationship may elucidate the molecular basis for considering cholesterol as a risk factor of aggressive prostate tumors, and underscore the potential of the dysfunctional ApoE2/E4 isoform as a biomarker of aggressive disease.
doi: 10.3892/ijo.2013.2057
PMCID: PMC3829771  PMID: 23934233
prostate cancer ;  apolipoprotein E ;  alleles ;  cholesterol ;  aggressive ;  caveolin-1 ;  polymorphism ;  genotype ;  phenotype
24.  The Role of Obesity in Cancer Survival and Recurrence 
Obesity and components of energy imbalance, i.e., excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included: 1) mechanisms associated with obesity and energy balance that influence cancer progression; 2) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; 3) associations between obesity and cancer risk, recurrence, and mortality; 4) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and 5) future directions.
doi:10.1158/1055-9965.EPI-12-0485
PMCID: PMC3415558  PMID: 22695735
neoplasms; obesity; diet; physical activity; survival; recurrence
25.  Harvest for Health Gardening Intervention Feasibility Study in Cancer Survivors 
Acta oncologica (Stockholm, Sweden)  2013;52(6):1110-1118.
Background
Cancer survivors are at increased risk for second malignancies, cardiovascular disease, diabetes, and functional decline. Evidence suggests that a healthful diet and physical activity may reduce the risk of chronic disease and improve health in this population.
Methods
We conducted a feasibility study to evaluate a vegetable gardening intervention that paired 12 adult and child cancer survivors with Master Gardeners to explore effects on fruit and vegetable intake, physical activity, quality-of-life, and physical function. Throughout the year-long study period, the survivor-Master Gardener dyads worked together to plan/plant 3 gardens, harvest/rotate plantings, and troubleshoot/correct problems. Data on diet, physical activity, and quality-of-life were collected via surveys; anthropometrics and physical function were objectively measured. Acceptability of the intervention was assessed with a structured debriefing survey.
Results
The gardening intervention was feasible (robust enrollment; minimal attrition) and well-received by cancer survivors and Master Gardeners. Improvement in 3 of 4 objective measures of strength, agility, and endurance was observed in 90% of survivors, with the following change scores (median [interquartile range]) noted between baseline and 1-year follow-up: hand grip test (+4.8 [3.0, 6.7] kg), 8 foot Get-Up-and-Go (−1.0 [−1.8, −0.2] seconds), 30-second chair stand (+3.0 [−1.0, 5.0] stands), and 6-minute walk (+38 [20, 160] feet). Increases of ≥1 fruit and vegetable serving/ day and ≥30 minutes/week of physical activity were observed in 40% and 60%, respectively.
Conclusion
These preliminary results support the feasibility and acceptability of a mentored gardening intervention and suggest that it may offer a novel and promising strategy to improve fruit and vegetable consumption, physical activity, and physical function in cancer survivors. A larger randomized controlled trial is needed to confirm our results.
doi:10.3109/0284186X.2013.770165
PMCID: PMC3718632  PMID: 23438359
cancer survivors; gardening; intervention; health; diet

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