Cancer is a disease of aging, and aged cancer patients have a poorer prognosis. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumor progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression1–4 we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. We find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signaling cascade in melanoma cells that results in a decrease in β-catenin and MITF, and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to ROS-induced DNA damage, rendering them more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumor progression, offering new paradigms for the design of therapy for the elderly.
Excess or rapid weight gain during the first 2 years of life is associated with an increased risk of later childhood and adult overweight and obesity. When compared with breastfed infants, formula fed infants are more likely to experience excess or rapid weight gain, and this increased risk in formula fed infant populations may be due to a number of different mechanisms. These mechanisms include the nutrient composition of the formula and the way formula is prepared and provided to infants. This systematic literature review examines the association between formula feeding practice and excess or rapid weight gain. This review explores these different mechanisms and provides practical recommendations for best practice formula feeding to reduce rapid weight gain. Eighteen studies are included in this review. The findings are complicated by the challenges in study design and accuracy of measurements. Nevertheless, there are some potential recommendations for best practice formula feeding that may reduce excess or rapid weight gain, such as providing formula with lower protein content, not adding cereals into bottles, not putting a baby to bed with a bottle, and not overfeeding formula. Although further well designed studies are required before more firm recommendations can be made.
We have previously shown that Wnt5A drives invasion in melanoma. We have also shown that Wnt5A promotes resistance to therapy designed to target the BRAFV600E mutation in melanoma. Here, we show that melanomas characterized by high levels of Wnt5A respond to therapeutic stress by increasing p21 and expressing classical markers of senescence, including positivity for senescence-associated β-galactosidase (SA-β-gal), senescence associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. We find that despite this, these cells retain their ability to migrate and invade. Further, despite the expression of classic markers of senescence like SA-β-gal and SAHF, these Wnt5A-high cells are able to colonize the lungs in in vivo tail-vein colony forming assays. This clearly underscores the fact that these markers do not indicate true senescence in these cells, but instead an adaptive stress response that allows the cells to evade therapy and invade. Notably, silencing Wnt5A reduces expression of these markers and decreases invasiveness. The combined data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance.
BackgroundInfant formula feeding practices are an important consideration for obesity prevention. An infant’s diet is influential on their later risk of developing overweight or obesity, yet very little is known about infant formula feeding practices. It is plausible that certain modifiable practices may put children at higher risk of developing overweight or obesity, for example how much and how often a baby is fed. Understanding how parents use infant formula and what factors may influence this practice is therefore important. Moreover, parents who feed their infants formula have identified a lack of support and access to resources to guide them. Therefore this study aimed to explore parents’ infant formula feeding practices to understand how parents use infant formula and what factors may influence this practice.MethodsUsing an explorative qualitative design, data were collected using semi-structured telephone interviews and analysed using a pragmatic inductive approach to thematic analysis.ResultsA total of 24 mothers from across Australia were interviewed. Mothers are influenced by a number of factors in relation to their infant formula feeding practice. These factors include information on the formula tin and marketing from formula manufacturers, particularly in relation to choosing the type of formula. Their formula feeding practices are also influenced by their interpretation of infant cues, and the amount of formula in the bottle. Many mothers would like more information to aid their practices but barriers exist to accessing health professional advice and support, so mothers may rely on informal sources. Some women reported that the social environment surrounding infant feeding wherein breastfeeding is promoted as the best option leads a feeling of stigma when formula feeding.ConclusionsAdditional support for parents’ feeding their infants with formula is necessary. Health professionals and policy around infant formula use should include how formula information may be provided to parents who use formula in ways that do not undermine breastfeeding promotion. Further observational research should seek to understand the interaction between advice, interpretation of cues and the amount formula fed to infants.Electronic supplementary materialThe online version of this article (10.1186/s12887-017-0977-7) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.