Mammary adipocytes promote breast tumor cell invasion and angiogenesis in the context of menopause and obesity.

The mechanism(s) underlying obesity-related postmenopausal (PM) breast cancer (BC) are not clearly understood. We hypothesized that the increased local presence of 'obese' mammary adipocytes within the BC microenvironment promotes the acquisition of an invasive and angiogenic BC cell phenotype and accelerates tumor proliferation and progression. BC cells, treated with primary mammary adipocyte secretome from premenopausal (Pre-M) and PM obese women (ObAdCM; obese adipocyte conditioned-media) upregulated the expression of several pro-tumorigenic factors including VEGF, lipocalin-2 and IL-6. Both Pre-M and PM ObAdCM stimulated endothelial cell recruitment and proliferation and significantly stimulated BC cell proliferation, migration and invasion. IL-6 and LCN2 induced STAT3/Akt signaling in BC cells and STAT3 inhibition abrogated the ObAdCM-stimulated BC cell proliferation and migration. Expression of proangiogenic regulators including VEGF, NRP1, NRP2, IL8RB, TGFß2, and TSP-1 were found to be differentially regulated in mammary adipocytes from obese PM women. Comparative RNAseq indicated an upregulation of PI3K/Akt signaling, ECM-receptor interactions and lipid/fatty acid metabolism in PM versus Pre-M mammary adipocytes. Our results demonstrate that irrespective of menopausal status, cross-talk between obese mammary adipocytes and BC cells promotes tumor aggressiveness and suggest that targeting the LCN2/IL-6/STAT3 signaling axis may be a useful strategy in obesity-driven breast tumorigenesis.

Escape from breast tumor dormancy: The convergence of obesity and menopause.

Obesity is associated with an increased risk of, and a poor prognosis for, postmenopausal (PM) breast cancer (BC). Our goal was to determine whether diet-induced obesity (DIO) promotes 1) shorter tumor latency, 2) an escape from tumor dormancy, and 3) an acceleration of tumor growth and to elucidate the underlying mechanism(s). We have developed in vitro assays and PM breast tumor models complemented by a noninvasive imaging system to detect vascular invasion of dormant tumors and have used them to determine whether obesity promotes the escape from breast tumor dormancy and tumor growth by facilitating the switch to the vascular phenotype (SVP) in PM BC. Obese mice had significantly higher tumor frequency, higher tumor volume, and lower overall survival compared with lean mice. We demonstrate that DIO exacerbates mammary gland hyperplasia and neoplasia, reduces tumor latency, and increases tumor frequency via an earlier acquisition of the SVP. DIO establishes a local and systemic proangiogenic and inflammatory environment via the up-regulation of lipocalin-2 (LCN2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) that may promote the escape from tumor dormancy and tumor progression. In addition, we show that targeting neovascularization via a multitargeted receptor tyrosine kinase inhibitor, sunitinib, can delay the acquisition of the SVP, thereby prolonging tumor latency, reducing tumor frequency, and increasing tumor-free survival, suggesting that targeting neovascularization may be a potential therapeutic strategy in obesity-associated PM BC progression. This study establishes the link between obesity and PM BC and, for the first time to our knowledge, bridges the dysfunctional neovascularization of obesity with the earliest stages of tumor development.

Changes in Package Sizes of Savoury Snacks through Exploration of Euromonitor and Industry Perspectives.

Portion sizes of many energy-dense and nutrient-poor foods and drinks have increased in the past decade, whereas our understanding of the pattern of changes in package sizes remains limited. This study aimed to determine changing trends in sales and package sizes of savoury snacks in Australia, the USA, Japan and Hong Kong, and to investigate industry perspectives for these changes. Sales data (units per capita) between 2006−2020 on savoury snacks were extracted from the Euromonitor International database. Industry perspectives on package size changes were extracted systematically from selected databases, company reports and related websites following the PRISMA-ScR guidelines. The findings showed that sales per capita of savoury snacks of all package sizes increased across all four countries/regions between 2006−2020. Although changes in the proportion of smaller (<100 g) versus larger (>100 g) package size sales in each country/region over time were modest, Japan and Hong Kong exhibited a consistently higher proportion of smaller package sales compared with Australia and the USA (83.3%, 64.4%, 44.3%, 20.2%, respectively). Industry perspectives showed that increasing consumer health consciousness, demands for convenience and portion control were the main contributors to decreasing package sizes of savoury snacks. Industry reports from 2020 showed an increase in larger package size sales due to consumer purchasing behaviour amidst the COVID-19 pandemic.

The Immediate Effect of Adding Lumbar Mobilization to A Static Stretching Program on Hamstrings Range of Motion: An Exploratory Study.

A contributing risk factor and a byproduct of a hamstrings strain is limited hamstrings range of motion (ROM). Some evidence supports static stretching (SS) and lumbar spinal mobilization therapy (LSMT) as an effective means for increasing hamstrings ROM. However, the efficacy of combining LSMT and SS for increasing hamstrings ROM is unknown. The objective of the study is to quantify the immediate effects of the combination of LSMT and SS compared to LSMT and SS on hamstrings ROM in a healthy population. Thirty participants were randomized by block allocation into one of three intervention groups: (1) LSMT (unilateral lumbar PA mobilization at L-4); (2) SS; or (3) combination of LSMT and SS. Hamstrings ROM was measured pre- and post-intervention by the active knee extension test (AKET). There was no group-by-time interaction effect (p = 0.871). Within group analysis revealed a significant statistical change and a large effect size: LSMT (p = .037, RCI = 3.36, d = 0.771); SS (p = 0.035, RCI = 2.94, d = 0.781); combination (p = .005, RCI = 4.21, d = 1.186. The findings suggest that the combination of LSMT and SS does not have a further effect on hamstrings ROM compared to the individual results of LSMT or SS.