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We present here two hepatocellular carcinoma (HCC) patients with gastrointestinal tract involvement (GITI). Hemorrhage due to duodenal involvement was the inaugural event of the HCC for the first patient. Dysphagia due to HCC recurrence in the oesophagus four years after left hepatectomy was the call symptom for the second. As incidence of HCC increases, and overall survival improves, incidence of GITI in HCC patients is expected to increase.

International audience; Au printemps 2013, des centaines de milliers de personnes manifestent dans plusieurs villes brésiliennes pour dénoncer la hausse des tarifs du transport public dans un contexte d’augmentation des dépenses publiques consacrées à l’organisation de la coupe du monde de football. En octobre 2018, en France, le mouvement dit « des gilets jaunes » émerge en réaction à la hausse du prix des carburants liée à l’application d’une taxe sur le carbone et à la diminution du seuil de vitesse autorisée sur les réseaux routiers interurbains. Mi-octobre 2019, au Chili, un mouvement social d’une ampleur sans précédent depuis la fin de la dictature se déploie à la suite d’une augmentation de plus de trois pourcents des tickets de métro dans la capitale. Dans les trois cas, l’augmentation du coût des déplacements constitue l’élément déclencheur de la colère sociale. Les protestations dénoncent, entre autres choses, des mesures qui portent atteinte à la liberté de circuler et aggravent les difficultés quotidiennes dans l’accès aux ressources essentielles.Dans un monde globalisé où les circulations de personnes, de marchandises, de capitaux, d’informations constituent l’un des socles des économies capitalistes, une pluralité d’associations, de collectifs, d’organisations, de personnes réclame le respect ou l’extension des droits à la mobilité. Alors que la mobilité est devenue une condition indispensable de participation à la vie sociale, les inégalités face à la mobilité restent en effet très marquées, mettant à mal l’idée d’un droit de circulation universel pourtant affirmé dans les déclarations et constitutions nationales et internationales. Ces inégalités s’expriment à différentes échelles spatiales, sous des formes diverses d’atteinte à la liberté de circulation, de déplacements forcés, de pratiques de mobilité très contraintes ou d’accès différenciés à l’espace public ou aux modes de transport. Dans ce contexte, la justice de la mobilité fait l’objet de revendications croissantes, s’impose dans les agendas politiques, se diffuse dans le débat public.Dans ce chapitre, nous proposons d’aborder la justice de la mobilité dans sa dimension politique, c’est-à-dire au regard des problématiques de pouvoir qu’elle révèle, aussi bien dans l’analyse des inégalités observées que dans les politiques ou dans les mouvements protestataires qui défendent des objectifs de justice de la mobilité. Pour ce faire, nous commençons par évoquer les principaux enjeux de la justice de la mobilité dans les sociétés occidentales contemporaines (1). Puis nous exposons les théories de la justice sociale les plus couramment appliquées à la mobilité (2). Dans un troisième temps, nous présentons les travaux de recherche majeurs appliqués à la justice de la mobilité et à ses implications politiques. Tout d’abord dans le domaine des transports et de la planification urbaine (3), puis dans le champ plus large des sciences sociales (4). En conclusion, nous revenons sur les controverses scientifiques et politiques autour des enjeux de la justice de la mobilité (5).

Cancers are heterogeneous multifactorial diseases consisting of a major public health issue worldwide. Sex disparities are evidenced in cancer incidence, mortality, expression of prognosis factor, response to treatment, and survival. For both sexes, an interplay of intrinsic and environmental factors influences cancer cells and tumor microenvironment (TME) components. The TME cumulates both supportive and communicative functions, contributing to cancer development, progression, and metastasis dissemination. The frontline topics of this chapter are focused on the contribution of sex, via steroid hormones, such as estrogens and androgens, on the following components of the TME: cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), blood and lymphatic endothelial cells, and immunity/inflammatory system.

Funder: Health Foundation's grant to THIS (The Healthcare Improvement Studies) Insitute at the University of Cambridge, Rationale, Aims and Objectives: Six years ago, the Supreme Court judgement in Montgomery v Lanarkshire changed medical law. It introduced a new patient‐based standard of care for the communication of treatment risks and alternatives, rejecting the doctor‐based standard that had long governed all aspects of medical negligence. This is the first systematic review to analyse the literature on Montgomery. Our aim is to appraise and synthesize the literature on Montgomery's impact on medicine and the law and to identify areas for further academic enquiry and implications for professional guidance and training. Methods: Searches were run in Medline, Embase, PsycINFO, Web of Science, Scopus, Westlaw UK, HeinOnline, and LexisNexis. Two reviewers screened papers. Extracted data was analysed and discussed by an interdisciplinary team. PRISMA guidelines were followed. Results: Of the 1134 papers identified, 100 met the inclusion criteria. These papers revealed significant disagreement on four core sets of issues, focusing on Montgomery's impact on: (1) legal and professional duties; (2) medical practice; (3) the patient experience; and (4) litigation. The first set addresses whether the case actually changed doctors' legal and professional duties, the relationship between GMC guidance and medical law, and the boundaries of Montgomery. The second explores whether the decision has incentivized defensive medicine, its resource implications, and doctors' knowledge of it. The third concerns whether and how the decision has promoted patient autonomy and involvement in their own care. The fourth focuses on whether the case has caused an increase in litigation. Conclusions: Despite the abundance of legal and medical literature on Montgomery, many issues remain unresolved. Empirical research is required for many of the questions. Doctrinal analysis informed by medical knowledge is also required to assess whether Montgomery may have unrecognized ramifications—for example, whether it will require the disclosure of risks associated with diagnostic uncertainty, where doctors advise patients without performing procedures.

Fungicides are used to suppress the growth of fungi for crop protection. The most widely used fungicides are succinate dehydrogenase inhibitors (SDHIs) that act by blocking succinate dehydrogenase, the complex II of the mitochondrial electron transport chain. As recent reports suggested that SDHI-fungicides could not be selective for their fungi targets, we tested the mitochondrial function of human cells (Peripheral Blood Mononuclear Cells or PBMCs, HepG2 liver cells, and BJ-fibroblasts) after exposure for a short time to Boscalid and Bixafen, the two most used SDHIs. Electron Paramagnetic Resonance (EPR) spectroscopy was used to assess the oxygen consumption rate (OCR) and the level of mitochondrial superoxide radical. The OCR was significantly decreased in the three cell lines after exposure to both SDHIs. The level of mitochondrial superoxide increased in HepG2 after Boscalid and Bixafen exposure. In BJ-fibroblasts, mitochondrial superoxide was increased after Bixafen exposure, but not after Boscalid. No significant increase in mitochondrial superoxide was observed in PBMCs. Flow cytometry revealed an increase in the number of early apoptotic cells in HepG2 exposed to both SDHIs, but not in PBMCs and BJ-fibroblasts, results consistent with the high level of mitochondrial superoxide found in HepG2 cells after exposure. In conclusion, short-term exposure to Boscalid and Bixafen induces a mitochondrial dysfunction in human cells.

(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe), (2) Methods: glucose consumption, lactate secretion and extracellular acidification rate (ECAR) were measured in vitro after exposure of cervix cancer SiHa cells and breast cancer 4T1 cells to UK-5099 (10 µM). Mice bearing the 4T1 tumor model were treated daily during four days with UK-5099 (3 mg/kg). The pHe was evaluated in vivo using either chemical exchange saturation transfer (CEST)-MRI with iopamidol as pHe reporter probe or 31P-NMR spectroscopy with 3-aminopropylphosphonate (3-APP). MR protocols were applied before and after 4 days of treatment, (3) Results: glucose consumption, lactate release and ECAR were increased in both cell lines after UK-5099 exposure. CEST-MRI showed a significant decrease in tumor pHe of 0.22 units in UK-5099-treated mice while there was no change over time for mice treated with the vehicle. Parametric images showed a large heterogeneity in response with 16% of voxels shifting to pHe values under 7.0. In contrast, 31P-NMR spectroscopy was unable to detect any significant variation in pHe, (4) Conclusions: MPC inhibition led to a moderate acidification of the extracellular medium in vivo. CEST-MRI provided high resolution parametric images (0.44 µL/voxel) of pHe highlighting the heterogeneity of response within the tumor when exposed to UK-5099.

Oestrogen signalling pathways are emerging targets for lung cancer therapy. Unravelling the contribution of oestrogens in lung cancer development is a pre-requisite to support the development of sex-based treatments and identify patients who could potentially benefit from anti-oestrogen treatments. In this study, we highlight the contribution of lymphatic and blood endothelia in the sex-dependent modulation of lung cancer. The orthotopic graft of syngeneic lung cancer cells into immunocompetent mice showed that lung tumours grow faster in female mice than in males. Moreover, oestradiol (E2) promoted tumour development, increased lymph/angiogenesis and VEGFA and bFGF levels in lung tumours of females through an oestrogen receptor (ER) alpha-dependent pathway. Furthermore, while treatment with ERb antagonist was inefficient, ERa antagonist (MPP) and tamoxifen decreased lung tumour volumes, altered blood and lymphatic vasculature and reduced VEGFA and bFGF levels in females, but not in males. Finally, the quantification of lymphatic and blood vasculature of lung adenocarcinoma biopsies from patients aged between 35 and 55 years revealed more extensive lymphangiogenesis and angiogenesis in tumour samples issued from women than from men. In conclusion, our findings highlight an E2/ERa-dependent modulation of lymphatic and blood vascular components of lung tumour microenvironment. Our study has potential clinical implication in a personalised medicine perspective by pointing to the importance of oestrogen status or supplementation on lung cancer development that should be considered to adapt therapeutic strategies., info:eu-repo/semantics/published

AIM: This study aimed at developing antibody-functionalized gold nanoparticles (AuNPs) to selectively target cancer cells and probing their potential radiosensitizing effects under proton irradiation.MATERIALS & METHODS: AuNPs were conjugated with cetuximab (Ctxb-AuNPs). Ctxb-AuNP uptake was evaluated by transmission electron microscopy and atomic absorption spectroscopy. Radioenhancing effect was assessed using conventional clonogenic assay.RESULTS & CONCLUSION: Ctxb-AuNPs specifically bound to and accumulated in EGFR-overexpressing A431 cells, compared with EGFR-negative MDA-MB-453 cells. Ctxb-AuNPs enhanced the effect of proton irradiation in A431 cells but not in MDA-MB-453 cells. These data indicate, for the first time, that combining enhanced uptake by specific targeting and radioenhancing effect, using conjugated AuNPs, is a promising strategy to increase cell killing by protontherapy.

Although cities globally are increasingly mobilizing re-naturing projects to address diverse urban socio-environmental and health challenges, there is mounting evidence that these interventions may also be linked to the phenomenon known as green gentrification. However, to date the empirical evidence on the relationship between greenspaces and gentrification regarding associations with different greenspace types remains scarce. This study focused on 28 mid-sized cities in North America and Western Europe. We assessed improved access to different types of greenspace (i.e. total area of parks, gardens, nature preserves, recreational areas or greenways [i] added before the 2000s or [ii] added before the 2010s) and gentrification processes (including [i] gentrification for the 2000s; [ii] gentrification for the 2010s; [iii] gentrification throughout the decades of the 2000s and 2010s) in each small geographical unit of each city. To estimate the associations, we developed a Bayesian hierarchical spatial model for each city and gentrification time period (i.e. a maximum of three models per city). More than half of our models showed that parks—together with other factors such as proximity to the city center—are positively associated with gentrification processes, particularly in the US context, except in historically Black disinvested postindustrial cities with lots of vacant land. We also find than in half of our models newly designated nature preserves are negatively associated with gentrification processes, particularly when considering gentrification throughout the 2000s and the 2010s and in the US. Meanwhile, for new gardens, recreational spaces and greenways, our research shows mixed results (some positive, some negative and some no effect associations). Considering the environmental and health benefits of urban re-naturing projects, cities should keep investing in improving park access while simultaneously implementing anti-displacement and inclusive green policies.

We report a case whereTo the best of our knowledge, this is the first case of

Simple Summary Hormonal treatments, especially those used to treat menopause symptoms are known to increase breast cancer risk. It is thus necessary to identify new formulations with a better benefit/risk profile. The aim of this translational study was to evaluate the breast cancer risk associated with a combination of a natural estrogen named estetrol, with progestogens such as natural progesterone and drospirenone. Since the assessment of breast cancer risk in patients during drug development is not possible given the requirement of long-term studies in large populations, this study provides new evidence that a therapeutic dose of estetrol for menopause treatment or contraception, combined with progesterone or drospirenone, may provide a better benefit/risk profile toward breast cancer risk compared to the hormonal treatments currently available for patients. Abstract Given the unequivocal benefits of menopause hormone therapies (MHT) and combined oral contraceptives (COC), there is a clinical need for new formulations devoid of any risk of breast cancer promotion. Accumulating data from preclinical and clinical studies support that estetrol (E4) is a promising natural estrogen for MHT and COC. Nevertheless, we report here that E4 remains active on the endometrium, even under a dose that is neutral on breast cancer growth and lung metastasis dissemination. This implies that a progestogen should be combined with E4 to protect the endometrium of non-hysterectomized women from hyperplasia and cancer. Through in vivo observations and transcriptomic analyses, our work provides evidence that combining a progestogen to E4 is neutral on breast cancer growth and dissemination, with very limited transcriptional impact. The assessment of breast cancer risk in patients during the development of new MHT or COC is not possible given the requirement of long-term studies in large populations. This translational preclinical research provides new evidence that a therapeutic dose of E4 for MHT or COC, combined with progesterone or drospirenone, may provide a better benefit/risk profile towards breast cancer risk compared to hormonal treatments currently available for patients.