Perturbateurs endocriniens et cancer : les bisphénols pourraient-ils avoir un impact sur l'initiation et la progression du cancer de la vessie?

Les bisphénols sont des composés synthétiques utilisés dans la synthèse des plastiques. Ils ont la capacité de se lier à plusieurs récepteurs cellulaires, dont certains récepteurs hormonaux, ce qui leur confère des propriétés de perturbateurs endocriniens. Certains de ces récepteurs hormonaux sont, entre autres, présents au niveau de l'urothélium de la vessie. De plus en plus d'études ont démontré que l'exposition aux bisphénols est associée à la progression tumorale, surtout pour les cancers hormono-dépendants tels que le cancer de la prostate. La vessie n'est pas considérée comme un tissu hormono-sensible, mais des études ont démontré le rôle des récepteurs hormonaux dans l'initiation et la progression de cancer de la vessie. Étant donné la présence de ces composés dans l'urine chez l'humain, nous avions pour objectif de déterminer si l'exposition chronique aux bisphénols pourrait avoir un impact sur l'initiation et la progression du cancer de la vessie. Ainsi, nous avons exposé des cellules urothéliales saines, des cellules cancéreuses non-invasives et cancéreuses invasives de vessie, des fibroblastes vésicaux et des fibroblastes associés au cancer à des concentrations physiologiques de bisphénols. Nous avons ensuite caractérisé l'impact de cette exposition sur le métabolisme énergétique et l'activité physiologique des cellules. Nous avons observé que les cellules urothéliales et stromales saines présentaient une diminution de ces caractéristiques par rapport aux contrôles, tandis que ces paramètres chez les cellules cancéreuses et les fibroblastes associés au cancer étaient augmentés. Ainsi, l'exposition chronique aux bisphénols semble favoriser la progression des cancers de vessie non-invasifs en cancers invasifs. Ce projet de recherche a permis d'apporter des informations novatrices sur l'impact de perturbateurs endocriniens sur le développement du cancer de la vessie.Bisphenols are synthetic compounds used to produce plastics. They can bind to several cell receptors, including some hormonal receptors, which confers them endocrine-disrupting properties. Some of these hormonal receptors can be found in the urothelium of the bladder. Studies have shown that exposure to bisphenols is associated with tumor progression, especially for hormone-dependent cancers such as prostate cancer. Although the bladder is not recognized as a hormone-sensitive tissue, studies have shown the role of hormonal receptors on bladder cancer initiation and progression. Since these compounds are found in most human urine samples, our objective was to determine whether chronic exposure to bisphenols could have an impact on the initiation and progression of bladder cancer. Therefore, we exposed healthy urothelial cells, non-invasive and invasive bladder cancer cells, bladder fibroblasts, and cancer-associated fibroblasts to physiological concentrations of bisphenols. We then characterized the impact of this exposure on the energy metabolism and physiological activity of the cells. We observed that healthy urothelial and stromal cells exhibited decreased characteristics compared to the controls, while these parameters were increased in cancer cells and cancer-associated fibroblasts. Thus, chronic exposure to bisphenols appears to promote the progression of non-invasive bladder cancers to invasive cancers. This research project provided innovative information on the impact of endocrine disruptors on the development of bladder cancer

Pour éviter de se noyer dans la (troisième) vague : réflexions sur l’histoire et l’actualité du féminisme radical

Ce texte a pour objet de reconnaître la présence et l’apport du féminisme radical autant dans l’histoire que dans l’actualité. Relégué aux oubliettes, jugé « dépassé » et « désuet », ne remportant supposément pas l’adhésion des « jeunes » femmes, le féminisme radical est dorénavant opposé à un « nouveau » féminisme, à une « troisième vague », prétendument portée par les « jeunes » féministes. La conceptualisation de cette « troisième vague » se base sur une typologie contestable – soit une fausse équation entre idées et périodes de militance – et également sur une volonté de « dépasser » la « deuxième vague », associée à un féminisme radical simplifié et empreint d’importantes idées fausses au point de vue théorique.The object of this text is to recognize the presence and the positive aspects of radical feminism in history as much as in the present. Relegated to dark places, judged old-fashioned and antiquated, apparently not winning the favors of “young women”, radical feminism is put in opposition to a “new feminism”, a “third wave” that is supposedly carried out by “young” feminists. The conceptualization of this “third wave” is grounded on a questionable typology – that of a false equation between ideas and activism periods – and a desire to move past the “second wave”, which is associated with a simplified and theoretically misconceived radical feminism

Heat-Inactivation of Fetal and Newborn Sera Did Not Impair the Expansion and Scaffold Engineering Potentials of Fibroblasts

Heat inactivation of bovine sera is routinely performed in cell culture laboratories. Nevertheless, it remains debatable whether it is still necessary due to the improvement of the production process of bovine sera. Do the benefits balance the loss of many proteins, such as hormones and growth factors, that are very useful for cell culture? This is even truer in the case of tissue engineering, the processes of which is often very demanding. This balance is examined here, from nine populations of fibroblasts originating from three different organs, by comparing the capacity of adhesion and proliferation of cells, their metabolism, and the capacity to produce the stroma; their histological appearance, thickness, and mechanical properties were also evaluated. Overall, serum inactivation does not appear to provide a significant benefit

Glucuronidated Metabolites of Bisphenols A and S Alter the Properties of Normal Urothelial and Bladder Cancer Cells

Bisphenol A (BPA) and bisphenol S (BPS) are synthetic chemicals used to produce plastics which can be released in food and water. Once ingested, BPA and BPS are metabolized by the liver, mainly as glucuronidated metabolites, and are excreted through urine. Since urine can be stored for many hours, the bladder is chronically exposed to BP metabolites, and studies have shown that these metabolites can remain active in the organism. Therefore, the effect of physiological concentrations of glucuronidated BPs was evaluated on the bioenergetics (glycolysis and mitochondrial respiration), migration and proliferation of normal urothelial cells, and non-invasive and invasive bladder cancer cells. The results demonstrated that an exposure of 72 h to glucuronidated BPA or BPS decreased the bioenergetics and activity of normal urothelial cells, while increasing these parameters for bladder cancer cells. These findings suggest that BP metabolites are not as inactive as initially believed, and their ubiquitous presence in the urine could promote bladder cancer progression

Bisphenol A Alters the Energy Metabolism of Stromal Cells and Could Promote Bladder Cancer Progression

Bisphenol A (BPA) is an endocrine-disrupting molecule used in plastics. Through its release in food and the environment, BPA can be found in humans and is mostly excreted in urine. The bladder is therefore continuously exposed to this compound. BPA can bind to multiple cell receptors involved in proliferation, migration and invasion pathways, and exposure to BPA is associated with cancer progression. Considering the physiological concentrations of BPA in urine, we tested the effect of nanomolar concentrations of BPA on the metabolism of bladder fibroblasts and cancer-associated fibroblasts (CAFs). Our results show that BPA led to a decreased metabolism in fibroblasts, which could alter the extracellular matrix. Furthermore, CAF induction triggered a metabolic switch, similar to the Warburg effect described in cancer cells. Additionally, we demonstrated that nanomolar concentrations of BPA could exacerbate this metabolic switch observed in CAFs via an increased glycolytic metabolism, leading to greater acidification of the extracellular environment. These findings suggest that chronic exposure to BPA could promote cancer progression through an alteration of the metabolism of stromal cells

Bisphenols and urological cancers

Bisphenols are endocrine-disrupting chemicals found in a broad range of products that can modulate hormonal signalling pathways and various other biological functions. These compounds can bind steroid receptors, e.g. estrogen and androgen receptors, expressed by numerous cells and tissues, including the prostate and the bladder, with the potential to alter their homeostasis and normal physiological functions. In the past years, exposure to bisphenols was linked to cancer progression and metastasis. As such, recent pieces of evidence suggest that endocrine-disrupting chemicals can lead to the development of prostate cancer. Moreover, bisphenols are found in the urine of the wide majority of the population. They could potentially affect the bladder's normal physiology and cancer development, even if the bladder is not recognized as a hormone-sensitive tissue. This review will focus on prostate and bladder malignancies, two urological cancers that share standard carcinogenic processes. The description of the underlying mechanisms involved in cell toxicity, and the possible roles of bisphenols in the development of prostate and bladder cancer, could help establish the putative roles of bisphenols on public health

Criteria for prioritizing best practices to implement in cognitive rehabilitation

Cognitive rehabilitation is a high priority area to address in acquired brain injury (ABI) care. A greater understanding of the criteria used by rehabilitation teams when prioritizing specific cognitive interventions for implementation could inform the development of effective strategies to move evidence into practice. Therefore, the objective of this qualitative study was to describe the criteria for prioritizing best practices to implement in cognitive rehabilitation post-ABI using a comprehensive implementation framework. As the first step in a multi-site integrated knowledge translation initiative, a consensus-building methodology, i.e., the Technique for Research of Information by Animation of a Group of Experts (TRIAGE), was used to prioritize practices to implement by three separate ABI rehabilitation teams (n = 8, 12 and 15 members). Transcripts of the teams’ TRIAGE consensual group discussions were analyzed using the Framework Method and mapped across the domains of the Consolidated Framework for Implementation Research. The most important criteria guiding priority setting in all the teams were the characteristics of the inner setting, the interventions, the individuals involved, and patients’ and families’ needs and resources. Particularly critical in prioritizing best practices to implement in the view of all the teams appeared to be the characteristics of the inner setting (e.g., implementation climate, readiness for implementation). Overall, the teams tended to prioritize practices that were partially known and used by a few clinicians but needed more systematic implementation through inter-professional collaboration. Rehabilitation teams should monitor these factors throughout the process from prioritization to implementation of the selected best practices in order to guide the tailoring of implementation strategies

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

Animal testing has long been used in science to study complex biological phenomena that cannot be investigated using two-dimensional cell cultures in plastic dishes. With time, it appeared that more differences could exist between animal models and even more when translated to human patients. Innovative models became essential to develop more accurate knowledge. Tissue engineering provides some of those models, but it mostly relies on the use of prefabricated scaffolds on which cells are seeded. The self-assembly protocol has recently produced organ-specific human-derived three-dimensional models without the need for exogenous material. This strategy will help to achieve the 3R principles