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Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity-Breast Cancer Links.
Bustamante-Marin, XM, Merlino, JL, Devericks, E, Carson, MS, Hursting, SD, Stewart, DA
Frontiers in endocrinology. 2021;:632284
Abstract
The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer.
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Personalized Nutrition as a Key Contributor to Improving Radiation Response in Breast Cancer.
Shastri, AA, Lombardo, J, Okere, SC, Higgins, S, Smith, BC, DeAngelis, T, Palagani, A, Hines, K, Monti, DA, Volpe, S, et al
International journal of molecular sciences. 2021;(1)
Abstract
Understanding metabolic and immune regulation inherent to patient populations is key to improving the radiation response for our patients. To date, radiation therapy regimens are prescribed based on tumor type and stage. Patient populations who are noted to have a poor response to radiation such as those of African American descent, those who have obesity or metabolic syndrome, or senior adult oncology patients, should be considered for concurrent therapies with radiation that will improve response. Here, we explore these populations of breast cancer patients, who frequently display radiation resistance and increased mortality rates, and identify the molecular underpinnings that are, in part, responsible for the radiation response and that result in an immune-suppressive tumor microenvironment. The resulting immune phenotype is discussed to understand how antitumor immunity could be improved. Correcting nutrient deficiencies observed in these populations should be considered as a means to improve the therapeutic index of radiation therapy.
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Sodium Selenite Alleviates Breast Cancer-Related Lymphedema Independent of Antioxidant Defense System.
Han, HW, Yang, EJ, Lee, SM
Nutrients. 2019;(5)
Abstract
Long-term surveillance is necessary to identify patients at risk of developing secondary lymphedema after breast cancer surgery. We assessed how sodium selenite supplementation would affect breast cancer-related lymphedema (BCRL) symptoms and parameters in association with antioxidant effects. A randomized, double-blind, controlled trial was conducted on 26 participants with clinical stage II to III BCRL. The control group (CTRL, n = 12) and selenium group (SE, n = 14) underwent five sessions of 0.9% saline and 500 μg sodium selenite (Selenase®) IV injections, respectively, within 2 weeks. All patients were educated on recommended behavior and self-administered manual lymphatic drainage. Clinical diagnosis on lymphedema by physicians, bioimpedance data, blood levels of oxidative markers, including glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), glutathione peroxidase activity (GSH-Px), and serum oxygen radical absorbance capacity (ORAC) levels, were investigated at timelines defined as baseline, 2-week, and follow-up. Sodium selenite increased whole blood selenium concentration in the SE group. Compared to the baseline, at 2 weeks, 75.0% of participants in clinical stage showed improvement, while there was no change in the CTRL group. At follow-up, 83.3% and 10.0% of the SE and CTRL, respectively, showed stage changes from III to II (p = 0.002). Extracellular water (ECW) ratios were significantly reduced at 2 weeks and follow-up, only in the SE group. Blood GSH, GSSG, GSH/GSSG ratio, MDA, and ORAC levels did not change by selenium supplementation. Sodium selenite improved diagnostic stages of BCRL along with ECW ratios, although the beneficial effect might not be related to its antioxidant activity. Selenite's effect on lymphedema may be associated with non-antioxidant properties, such as anti-inflammation and immune function. Further mechanistic research using a larger population is needed.
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Repercussions of breastfeeding by diabetic women for breast cancer.
Franca, EL, Franca-Botelho, Ado C, Franca, JL, Ferrari, CK, Honorio-Franca, AC
Asian Pacific journal of cancer prevention : APJCP. 2013;(11):6233-9
Abstract
Diabetes represents a serious health problem. In the diabetic state, alterations in metabolism, increased susceptibility to infections and immunological changes occur. The suppression of the immune response has been identified as a relevant factor that contributes to the increase in the rate of infections in these patients. At the same time, breast cancer is the most frequent malignant tumor in women. The molecular and cellular mechanisms underlying cancer development have revealed that immune cells functionally regulate epithelial cancer development and progression. Breastfeeding has been hypothesized to reduce the risk of breast cancer. However, early systematic reviews have not yielded consistent findings for this association. The demand for human milk is increasing due to the promotion and consumer acceptance of the health benefits of consuming a natural product rich in bioactive components. However, due to changes in glucose metabolism, the components of the milk from diabetic women are modified depending on the time of evaluation. In this literature review, we summarize important new findings revealing the paradoxical role of breastfeeding in preventing the onset of breast cancer in diabetic mothers. We hypothesized that the milk component production in diabetic mothers is affected by changes in glucose metabolism. Therefore, adequate maternal glycemic control and an adequate duration of breastfeeding for diabetic mothers are crucial to ensure that the immunity components are able to confer protection against breast cancer.
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Blood peptidome-degradome profile of breast cancer.
Shen, Y, Tolić, N, Liu, T, Zhao, R, Petritis, BO, Gritsenko, MA, Camp, DG, Moore, RJ, Purvine, SO, Esteva, FJ, et al
PloS one. 2010;(10):e13133
Abstract
BACKGROUND Cancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients. METHODOLOGY AND PRINCIPAL FINDINGS The peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP) and age, race, and menopausal status matched control healthy persons (HP) were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins. CONCLUSIONS Degradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility.