Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous-65% to 85% of heart rate maximum-aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic minorities. Adherence to the intervention was 95%, and postintervention assessments were available in 91% of participants. Postintervention metabolic syndrome z-score was significantly improved in exercise versus usual care (between-group difference, -4.4; 95% CI, -5.9 to -2.7; P < .001). Sarcopenic obesity (appendicular skeletal mass index, P = .001; body mass index, P = .001) and circulating biomarkers, including insulin ( P = .002), IGF-1 ( P = .001), leptin ( P = .001), and adiponectin ( P = .001), were significantly improved postintervention compared with usual care. At 3-month follow-up, all metabolic syndrome variables remained significantly improved compared with baseline in the exercise group ( P < .01). Conclusion Combined resistance and aerobic exercise effectively attenuated metabolic syndrome, sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of sedentary, overweight, or obese survivors of breast cancer. Our findings suggest a targeted exercise prescription for improving metabolic syndrome in survivors of breast cancer and support the incorporation of supervised clinical exercise programs into breast cancer treatment and survivorship care plans.
BackgroundExercise is an effective strategy to improve quality of life and physical fitness in breast cancer survivors; however, few studies have focused on the early survivorship period, minorities, physically inactive and obese women, or tested a combined exercise program and measured bone health. Here, we report the effects of a 16-week aerobic and resistance exercise intervention on patient-reported outcomes, physical fitness, and bone health in ethnically diverse, physically inactive, overweight or obese breast cancer survivors.MethodsOne hundred breast cancer survivors within 6 months of completing adjuvant treatment were assessed at baseline, post-intervention, and 3-month follow-up (exercise group only) for physical fitness, bone mineral density, serum concentrations of bone biomarkers, and quality of life. The exercise intervention consisted of moderate-vigorous (65–85% heart rate maximum) aerobic and resistance exercise thrice weekly for 16 weeks. Differences in mean changes for outcomes were evaluated using mixed-model repeated measure analysis.ResultsAt post-intervention, the exercise group was superior to usual care for quality of life (between group difference: 14.7, 95% CI: 18.2, 9.7; p < 0.001), fatigue (p < 0.001), depression (p < 0.001), estimated VO2max (p < 0.001), muscular strength (p < 0.001), osteocalcin (p = 0.01), and BSAP (p = 0.001). At 3-month follow-up, all patient-reported outcomes and physical fitness variables remained significantly improved compared to baseline in the exercise group (p < 0.01).ConclusionsA 16-week combined aerobic and resistance exercise program designed to address metabolic syndrome in ethnically-diverse overweight or obese breast cancer survivors also significantly improved quality of life and physical fitness. Our findings further support the inclusion of supervised clinical exercise programs into breast cancer treatment and care.Trial registrationThis trial is registered on ClinicalTrials.gov: NCT01140282 as of June 9, 2010.
Purpose of Review Obesity is a recognized risk factor for the development of breast cancer and recurrence even when patients are treated appropriately. We reviewed the literature that addresses the impact of obesity on diagnosis and the individual therapeutic interventions, and present a summary of the findings. Recent Findings Compared to non-obese women with breast cancer, obese women with breast cancer have a worse disease-free and overall survival despite appropriate local and systemic therapies. In brief, obese breast cancer patients experience more complications related to surgery, radiation, and chemotherapy. Further, obese patients are at increased risk for local recurrence compared to normal-weight women. Similarly, systemic chemotherapy is less effective, even when dosed appropriately on the basis of actual weight. Overall, endocrine therapy is less effective in obese women, and there is a suggestion that aromatase inhibitors may be selectively less effective than tamoxifen. Obese women are less likely to undergo breast reconstruction than normal-weight women, and those who do have surgery experience more surgical complications. Summary The efficacy of cancer treatments is significantly lower in obese breast cancer survivors, posing greater challenges in patient care and disease management in this patient population. Further investigations are warranted to assess the effects on treatment outcomes and optimize therapeutic mechanisms in order to successfully target breast cancer associated with obesity.
Alternative mRNA splicing is a fundamental process of gene regulation via the precise control of the post-transcriptional step that occurs before mRNA translation. Errors in RNA splicing have been known to correlate with different diseases; however, a key limitation is the lack of technologies for live cell monitoring and quantification to understand the process of alternative splicing. Here, we report a spectroscopic strategy for quantitative imaging of mRNA splice variants in living cells, using nanoplasmonic dimer antennas. The spatial and temporal distribution of three selected splice variants of the breast cancer susceptibility gene, BRCA1 were monitored at single copy resolution by measuring the hybridization dynamics of nanoplasmonic antennas targeting complementary mRNA sequences in live cells. Our study provides valuable insights on RNA and its transport in living cells, which has the potential to enhance our understanding of cellular protein complex, pharmacogenomics, genetic diagnosis, and gene therapies.
A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.
The identification and timely detection of pathogenic bacteria is critical to ensuring safe food, health, and water. Although surface enhanced Raman scattering (SERS) methods have been used for pathogen characterization and single molecule sensing, the challenge of detecting pathogens in very low numbers using an optimal substrate that is sensitive and reproducible is still a challenge. In this report, we have developed and explored a novel SERS active substrate of 60-80 nm diameter through the assembly of Ag nanocrystals (AgNCs) into Ag nanospheres (AgNSs). A finite difference time domain (FDTD) analysis of the electromagnetic field produced by these structures and the enhancement factor calculations indicated that an enhancement of 10 8 was possible using the 633 or 785 nm excitation. The exact enhancement factors (EF) through the experimental results were calculated to be 2.47 × 10 7 , which is close to that obtained through the FDTD analysis. Preliminary characterization of the SERS substrate was demonstrated using various labels from the fluorescent dye and nonfluorescent small molecules. More importantly, these novel SERS active substrates when used for pathogenic bacteria detection could detect cells as few as 10 colony forming units/mL (CFU/ mL). Using canonical variate analysis (CVA) in conjunction with Raman spectra, differentiation of three key pathogens (E. coli O157, S. typhimurium, and S. aureus) including live and dead cells was also accomplished. With further optimization of the SERS substrate, single cell detection is possible.
Effective identification of breast cancer stem cells (CSC) benefits from a multiplexed approach to detect cell surface markers that can distinguish this subpopulation, which can invade and proliferate at sites of metastasis. We present a new approach for dual-mode sensing based on targeting using pointer and signal enhancement using enhancer particle networks for detection by surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS). We demonstrate our concept to detect cell surface markers, CD44 and CD24, in three breast cancer cell lines to identify a CD44+/CD24- subpopulation of CSCs. The designed network structure can be well-controlled and has improved sensitivity compared to conventional approaches with ability to detect a single target on the membrane of a living cell. We have also developed a fractal approach to model the dimension of the network structure and developed an empirical relationship to estimate the number of particles in the network and its size. The empirical equation was validated with experiments and finite-difference time-domain simulations, and the cell phenotyping results were found to be in good agreement with published data from conventional sorting by flow cytometry.
A multicomponent nanostructure comprising of gold nanorod-nanoparticle (AuNR-AuNP) composites was fabricated to detect thrombin at subnanomolar concentrations in diluted human blood serum. Simulation and experiments revealed that the strong electromagnetic coupling resonance at the nanorod-nanoparticle junction of these probes can be used to construct highly sensitive SERS aptasensors.
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