RESUMEN
In addition to the major subcutaneous and visceral adipose tissues (AT), other adipose depots are dispersed throughout the body and are found in close interaction with proximal organs such as mammary and periprostatic AT (MAT and PPAT respectively). These ATs have an effect on proximal organ function during physiological processes and diseases such as cancer. We highlighted here some of their most distinctive features in terms of tissular organization and responses to external stimuli and discussed how obesity affects them based on our current knowledge.
Asunto(s)
Tejido Adiposo , Obesidad , Humanos , Tejido Adiposo/fisiología , Femenino , Obesidad/fisiopatología , Neoplasias/patología , Animales , Mama/fisiología , Mama/patología , Neoplasias de la Mama/patología , Glándulas Mamarias Humanas/fisiología , Glándulas Mamarias Humanas/patología , Grasa Intraabdominal , Grasa Subcutánea/fisiología , Grasa Subcutánea/patologíaRESUMEN
Poor air quality is the largest environmental health risk in England. In the West Midlands, UK, â¼2.9 million people are affected by air pollution with an average loss in life expectancy of up to 6 months. The 2021 Environment Act established a legal framework for local authorities in England to develop regional air quality plans, generating a policy need for predictive environmental impact assessment tools. In this context, we developed a novel Air Quality Lifecourse Assessment Tool (AQ-LAT) to estimate electoral ward-level impacts of PM2.5 and NO2 exposure on outcomes of interest to local authorities, namely morbidity (asthma, coronary heart disease (CHD), stroke, lung cancer), mortality, and associated healthcare costs. We apply the Tool to assess the health economic burden of air pollutant exposure and estimate benefits that would be generated by meeting WHO 2021 Global Air Quality Guidelines (AQGs) (annual average concentrations) for NO2 (10 µg/m3) and PM2.5 (5 µg/m3) in the West Midlands Combined Authority Area. All West Midlands residents live in areas which exceed WHO AQGs, with 2070 deaths, 2070 asthma diagnoses, 770 CHD diagnoses, 170 lung cancers and 650 strokes attributable to air pollution exposure annually. Reducing PM2.5 and NO2 concentrations to WHO AQGs would save 10,700 lives reducing regional mortality by 1.8%, gaining 92,000 quality-adjusted life years (QALYs), and preventing 20,500 asthma, 7400 CHD, 1400 lung cancer, and 5700 stroke diagnoses, with economic benefits of £3.2 billion over 20 years. Significantly, we estimate 30% of QALY gains relate to reduced disease burden. The AQ-LAT has major potential to be replicated across local authorities in England and applied to inform regional investment decisions.
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Contaminantes Atmosféricos , Contaminación del Aire , Exposición a Riesgos Ambientales , Material Particulado , Contaminación del Aire/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Humanos , Inglaterra , Material Particulado/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Neoplasias Pulmonares , Asma , Mejoramiento de la Calidad , Dióxido de Nitrógeno/análisis , Evaluación del Impacto en la Salud , Enfermedad Coronaria , Accidente CerebrovascularRESUMEN
Obesity is a negative prognosis factor for breast cancer. Yet, the biological mechanisms underlying this effect are still largely unknown. An emerging hypothesis is that the transfer of free fatty acids (FFA) between adipocytes and tumor cells might be altered under obese conditions, contributing to tumor progression. Currently there is a paucity of models to study human mammary adipocytes (M-Ads)-cancer crosstalk. As for other types of isolated white adipocytes, herein, we showed that human M-Ads die within 2-3 days by necrosis when grown in 2D. As an alternative, M-Ads were grown in a fibrin matrix, a 3D model that preserve their distribution, integrity and metabolic function for up to 5 days at physiological glucose concentrations (5 mM). Higher glucose concentrations frequently used in in vitro models promote lipogenesis during M-Ads culture, impairing their lipolytic function. Using transwell inserts, the matrix embedded adipocytes were cocultured with breast cancer cells. FFA transfer between M-Ads and cancer cells was observed, and this event was amplified by obesity. Together these data show that our 3D model is a new tool for studying the effect of M-Ads on tumor cells and beyond with all the components of the tumor microenvironment including the immune cells.
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Adipocitos , Neoplasias de la Mama , Ácidos Grasos no Esterificados , Glándulas Mamarias Humanas , Obesidad , Delgadez , Técnicas de Cultivo Tridimensional de Células , Adipocitos/metabolismo , Adipocitos/patología , Cultivo Primario de Células , Glándulas Mamarias Humanas/patología , Neoplasias de la Mama/patología , Obesidad/metabolismo , Obesidad/patología , Delgadez/metabolismo , Delgadez/patología , Humanos , Células MDA-MB-231 , Ácidos Grasos no Esterificados/metabolismo , PronósticoRESUMEN
Bone marrow adipose tissues (BMATs) and their main cellular component, bone marrow adipocytes (BMAds), are found within the bone marrow (BM), which is a niche for the development of hematological malignancies as well as bone metastasis from solid tumors such as breast and prostate cancers. In humans, BMAds are present within the hematopoietic or "red" BMAT and in the "yellow" BMAT where they are more densely packed. BMAds are emerging as new actors in tumor progression; however, there are many outstanding questions regarding their precise role. In this review, we summarized our current knowledge regarding the development, distribution, and regulation by external stimuli of the BMATs in mice and humans and addressed how obesity could affect these traits. We then discussed the specific metabolic phenotype of BMAds that appear to be different from "classical" white adipocytes, since they are devoid of lipolytic function. According to this characterization, we presented how tumor cells affect the in vitro and in vivo phenotype of BMAds and the signals emanating from BMAds that are susceptible to modulate tumor behavior with a specific emphasis on their metabolic crosstalk with cancer cells. Finally, we discussed how obesity could affect this crosstalk. Deciphering the role of BMAds in tumor progression would certainly lead to the identification of new targets in oncology in the near future.
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Adipocitos , Células de la Médula Ósea , Neoplasias , Adipocitos/metabolismo , Adipocitos/patología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Humanos , Masculino , Ratones , Neoplasias/patología , Obesidad/complicacionesRESUMEN
For the National Association of Paramedic School Directors, it is necessary to have reliable data in order to participate in the development of public health policies, but also to demonstrate the importance of investing in primary care through nursing leadership, training and competence in the service of populations. In France, nursing training capacities are increasing, university recognition is underway, and efforts have been made to finance training and increase salaries. These orientations need to be strengthened at the risk of not guaranteeing the stability of the workforce in the care sector.
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Liderazgo , Estudiantes , Francia , HumanosRESUMEN
White adipose tissue accumulates at various sites throughout the body, some adipose tissue depots exist near organs whose function they influence in a paracrine manner. Prostate gland is surrounded by a poorly characterized adipose depot called periprostatic adipose tissue (PPAT), which plays emerging roles in prostate-related disorders. Unlike all other adipose depots, PPAT secretes proinflammatory cytokines even in lean individuals and does not increase in volume during obesity. These unique features remain unexplained because of the poor structural and functional characterization of this tissue. This study characterized the structural organization of PPAT in patients compared with abdominopelvic adipose tissue (APAT), an extraperitoneal adipose depot, the accumulation of which is correlated to body mass index. Confocal microscopy followed by three-dimensional reconstructions showed a sparse vascular network in PPAT when compared with that in APAT, suggesting that this tissue is hypoxic. Unbiased comparisons of PPAT and APAT transcriptomes found that most differentially expressed genes were related to the hypoxia response. High levels of the hypoxia-inducible factor 2α confirmed the presence of an adaptive response to hypoxia in PPAT. This chronic hypoxic state was associated with inflammation and fibrosis, which were not further up-regulated by obesity. This fibrosis and inflammation explain the failure of PPAT to expand in obesity and open new mechanistic avenues to explain its role in prostate-related disorders, including cancer.
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Tejido Adiposo , Obesidad , Tejido Adiposo/patología , Fibrosis , Humanos , Hipoxia/patología , Inflamación/patología , Masculino , Obesidad/complicacionesRESUMEN
Obesity is a recognized factor for increased risk and poor prognosis of many cancers, including melanoma. In this study, using genetically engineered mouse models of melanoma (NrasQ61K transgenic expression, associated or not with Cdkn2a heterozygous deletion), we show that obesity increases melanoma initiation and progression by supporting tumor growth and metastasis, thereby reducing survival. This effect is associated with a decrease in p16INK4A expression in tumors. Mechanistically, adipocytes downregulate p16INK4A in melanoma cells through ß-catenin-dependent regulation, which increases cell motility. Furthermore, ß-catenin is directly transferred from adipocytes to melanoma cells in extracellular vesicles, thus increasing its level and activity, which represses CDKN2A transcription. Adipocytes from individuals with obesity have a stronger effect than those from lean individuals, mainly owing to an increase in the number of vesicles secreted, thus increasing the amount of ß-catenin delivered to melanoma cells and, consequently, amplifying their effect. In conclusion, in this study, we reveal that adipocyte extracellular vesicles control p16INK4A expression in melanoma, which promotes tumor progression. This work expands our understanding of the cooperation between adipocytes and tumors, particularly in obesity.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina , Vesículas Extracelulares , Melanoma , Obesidad , Adipocitos/metabolismo , Animales , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Vesículas Extracelulares/metabolismo , Melanoma/genética , Melanoma/metabolismo , Ratones , Obesidad/genética , Obesidad/metabolismo , beta Catenina/metabolismoRESUMEN
Primary human bone marrow adipocytes (BM-Ads) display a specific metabolism that is not recapitulated by in vitro differentiated bone marrow mesenchymal stromal cells. These findings highlight the need for using primary BM-Ads in studies of the metabolic impact of BM-Ads on surrounding cells. Here, we present a protocol for isolating human BM-Ads from bone marrow aspirates and verifying adipocyte suspension purity. These isolated and purified BM-Ads can be used for functional assays or frozen for molecular analyses. For complete details on the use and execution of this protocol, please refer to Attane et al. (2020).
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Adipocitos/citología , Células de la Médula Ósea/citología , Fémur/citología , Técnica del Anticuerpo Fluorescente , Humanos , Reproducibilidad de los ResultadosRESUMEN
Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated.
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Adipocitos/metabolismo , Adipocitos/patología , Médula Ósea/patología , Huesos/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores CCR3/metabolismo , Envejecimiento/patología , Médula Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Línea Celular Tumoral , Quimiocina CCL7/metabolismo , Quimiotaxis/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Humanos , Masculino , Metástasis de la Neoplasia , Obesidad/complicaciones , Neoplasias de la Próstata/complicacionesRESUMEN
Obesity is a major worldwide public health issue that increases the risk to develop cardiovascular diseases, type-2 diabetes, and liver diseases. Obesity is characterized by an increase in adipose tissue (AT) mass due to adipocyte hyperplasia and/or hypertrophia, leading to profound remodeling of its three-dimensional structure. Indeed, the maximal capacity of AT to expand during obesity is pivotal to the development of obesity-associated pathologies. This AT expansion is an important homeostatic mechanism to enable adaptation to an excess of energy intake and to avoid deleterious lipid spillover to other metabolic organs, such as muscle and liver. Therefore, understanding the structural remodeling that leads to the failure of AT expansion is a fundamental question with high clinical applicability. In this article, we describe a simple and fast clearing method that is routinely used in our laboratory to explore the morphology of mouse and human white adipose tissue by fluorescent imaging. This optimized AT clearing method is easily performed in any standard laboratory equipped with a chemical hood, a temperature-controlled orbital shaker and a fluorescent microscope. Moreover, the chemical compounds used are readily available. Importantly, this method allows one to resolve the 3D AT structure by staining various markers to specifically visualize the adipocytes, the neuronal and vascular networks, and the innate and adaptive immune cells distribution.
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Tejido Adiposo/patología , Imagenología Tridimensional , Salicilatos/farmacocinética , Adipocitos/metabolismo , Adipocitos/patología , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Humanos , Ratones , Microscopía Fluorescente , Obesidad/metabolismo , Obesidad/patologíaRESUMEN
Over the past decade, it has become apparent that metabolic reprogramming is a key event in tumor progression. The tumor microenvironment (TME) is a source of metabolites for tumor cells. Lipid-filled mature adipocytes are frequently found in proximity to invasive human tumors and release free fatty acids (FFAs) through lipolysis. These FFAs are taken up by tumor cells and used to promote tumor progression by mechanisms that include mitochondrial fatty acid oxidation (FAO). This review discusses recent advances in our understanding of this metabolic symbiosis between adipocytes and cancer cells and underlines the differences in this metabolic crosstalk between the various types of cancer and their localization.
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Adipocitos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Lipólisis , Neoplasias/patología , Microambiente Tumoral , Adipocitos/citología , Progresión de la Enfermedad , Metabolismo Energético , Vesículas Extracelulares/metabolismo , Humanos , Lipasa/metabolismo , Gotas Lipídicas/metabolismo , Mitocondrias/metabolismo , Oxidación-ReducciónRESUMEN
We analyze the combined effect of political violence and adverse climatic and health shocks on child nutrition using longitudinal data from Andhra Pradesh, India. The paper shows three key results using two-stage least square (2SLS) models: (i) the presence of political violence reduces the mean height-for-age z-scores of children by between 0.4 and 0.9 standard deviations and reduces the mean weight-for-age z-scores of children by between 0.3 and 0.6 standard deviations; (ii) political violence generates such a large negative effect on the long-term nutrition of children (measured by height-for-age z-scores) through a reduction of the ability of households to cope with drought and illness; and (iii) drought and illness have an adverse effect on child nutrition in Andhra Pradesh only in violence-affected communities. The 2SLS results are robust to a wide range of robustness tests. Potential mechanisms explaining the strong joint welfare effect of conflict and adverse shocks are the failure of economic coping strategies in areas of violence and restricted access to public goods and services.
Asunto(s)
Trastornos de la Nutrición del Niño/epidemiología , Política , Violencia/estadística & datos numéricos , Adaptación Psicológica , Pesos y Medidas Corporales , Niño , Preescolar , Sequías , Femenino , Humanos , India/epidemiología , Lactante , Masculino , Estado NutricionalRESUMEN
Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.
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Adipocitos/citología , Vesículas Extracelulares/metabolismo , Ácidos Grasos/metabolismo , Melanoma/metabolismo , Obesidad/complicaciones , Células 3T3 , Adipocitos/metabolismo , Animales , Autofagia , Línea Celular Tumoral , Movimiento Celular , Humanos , Metabolismo de los Lípidos , Masculino , Ratones , Mitocondrias/metabolismo , Dinámicas Mitocondriales , Obesidad/metabolismo , Oxidación-ReducciónRESUMEN
Under caloric restriction, bone marrow adipocytes (BM-Ads) do not decrease in size compared to white adipocytes, suggesting they harbor unique metabolic properties. We compare human primary BM-Ads with paired subcutaneous adipocytes (SC-Ads) using proteomic and lipidomic approaches. We find that, although SC-Ads and BM-Ads share similar morphological features, they possess distinct lipid metabolism. Although BM-Ad shows enrichment in proteins involved in cholesterol metabolism, correlating with increased free cholesterol content, proteins involved in lipolysis were downregulated. In particular, monoacylglycerol lipase expression is strongly reduced in BM-Ads, leading to monoacylglycerol accumulation. Consequently, basal and induced lipolytic responses are absent in BM-Ads, affirming their differences in metabolic fitness upon caloric restriction. These specific metabolic features are not recapitulated in vitro using common protocols to differentiate bone marrow mesenchymal stem cells. Thus, contrary to classical SC-Ads, BM-Ads display a specific lipid metabolism, as they are devoid of lipolytic activity and exhibit a cholesterol-orientated metabolism.
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Adipocitos/metabolismo , Médula Ósea/metabolismo , Metabolismo de los Lípidos , Proteoma/metabolismo , Adipocitos/citología , Adipocitos/enzimología , Adipocitos/ultraestructura , Animales , Médula Ósea/enzimología , Restricción Calórica , Línea Celular , Células Cultivadas , Colesterol/metabolismo , Humanos , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Lipólisis/fisiología , Ratones , Microscopía Electrónica de Transmisión , Monoacilglicerol Lipasas/genética , Monoacilglicerol Lipasas/metabolismo , Mapas de Interacción de Proteínas/genética , Mapas de Interacción de Proteínas/fisiología , Proteoma/genética , ProteómicaRESUMEN
Metabolic reprogramming represents an important hallmark of cancer cells. Besides de novo fatty acid synthesis, it is now clear that cancer cells can acquire Fatty Acids (FA) from tumor-surrounding adipocytes to increase their invasive capacities. Indeed, adipocytes release FA in response to tumor secreted factors that are transferred to tumor cells to be either stored as triglycerides and other complex lipids or oxidized in mitochondria. Like all cells, FA can be released over time from triglyceride stores through lipolysis and then oxidized in mitochondria in cancer cells. This metabolic interaction results in specific metabolic remodeling in cancer cells, and underpins adipocyte stimulated tumor progression. Lipolysis and fatty acid oxidation therefore represent novel targets of interest in the treatment of cancer. In this review, we summarize the recent advances in our understanding of the metabolic reprogramming induced by adipocytes, with a focus on breast cancer. Then, we recapitulate recent reports studying the effect of lipolysis and fatty acid oxidation inhibitors on tumor cells and discuss the interest to target these metabolic pathways as new therapeutic approaches for cancer.
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Adipocitos , Lipólisis , Ácidos Grasos , Metabolismo de los Lípidos , TriglicéridosRESUMEN
INTRODUCTION: Clinical studies suggest that obesity, in addition to promoting breast cancer aggressiveness, is associated with a decrease in chemotherapy efficacy, although the mechanisms involved remain elusive. As chemotherapy is one of the main treatments for aggressive or metastatic breast cancer, we investigated whether adipocytes can mediate resistance to doxorubicin (DOX), one of the main drugs used to treat breast cancer, and the mechanisms associated. METHODS: We used a coculture system to grow breast cancer cells with in vitro differentiated adipocytes as well as primary mammary adipocytes isolated from lean and obese patients. Drug cellular accumulation, distribution, and efflux were studied by immunofluorescence, flow cytometry, and analysis of extracellular vesicles. Results were validated by immunohistochemistry in a series of lean and obese patients with cancer. RESULTS: Adipocytes differentiated in vitro promote DOX resistance (with cross-resistance to paclitaxel and 5-fluorouracil) in a large panel of human and murine breast cancer cell lines independently of their subtype. Subcellular distribution of DOX was altered in cocultivated cells with decreased nuclear accumulation of the drug associated with a localized accumulation in cytoplasmic vesicles, which then are expelled into the extracellular medium. The transport-associated major vault protein (MVP), whose expression was upregulated by adipocytes, mediated both processes. Coculture with human mammary adipocytes also induced chemoresistance in breast cancer cells (as well as the related MVP-induced DOX efflux) and their effect was amplified by obesity. Finally, in a series of human breast tumors, we observed a gradient of MVP expression, which was higher at the invasive front, where tumor cells are at close proximity to adipocytes, than in the tumor center, highlighting the clinical relevance of our results. High expression of MVP in these tumor cells is of particular interest since they are more likely to disseminate to give rise to chemoresistant metastases. CONCLUSIONS: Collectively, our study shows that adipocytes induce an MVP-related multidrug-resistant phenotype in breast cancer cells, which could contribute to obesity-related chemoresistance.
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Adipocitos/metabolismo , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Obesidad/complicaciones , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Células 3T3 , Tejido Adiposo/citología , Adulto , Anciano , Animales , Antineoplásicos/uso terapéutico , Mama/citología , Mama/patología , Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Línea Celular Tumoral , Técnicas de Cocultivo , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Humanos , Mastectomía , Ratones , Persona de Mediana Edad , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Cultivo Primario de Células , ARN Interferente Pequeño/metabolismo , Partículas Ribonucleoproteicas en Bóveda/genéticaRESUMEN
Prostate gland is surrounded by periprostatic adipose tissue (PPAT), which is increasingly believed to play a paracrine role in prostate cancer progression. Our previous work demonstrates that adipocytes promote homing of prostate cancer cells to PPAT and that this effect is upregulated by obesity. Here, we show that once tumor cells have invaded PPAT (mimicked by an in vitro model of coculture), they establish a bidirectional crosstalk with adipocytes, which promotes tumor cell invasion. Indeed, tumor cells induce adipocyte lipolysis and the free fatty acids (FFA) released are taken up and stored by tumor cells. Incubation with exogenous lipids also stimulates tumor cell invasion, underlining the importance of lipid transfer in prostate cancer aggressiveness. Transferred FFAs (after coculture or exogenous lipid treatment) stimulate the expression of one isoform of the pro-oxidant enzyme NADPH oxidase, NOX5. NOX5 increases intracellular reactive oxygen species (ROS) that, in turn, activate a HIF1/MMP14 pathway, which is responsible for the increased tumor cell invasion. In obesity, tumor-surrounding adipocytes are more prone to activate the depicted signaling pathway and to induce tumor invasion. Finally, the expression of NOX5 and MMP14 is upregulated at the invasive front of human tumors where cancer cells are in close proximity to adipocytes and this process is amplified in obese patients, underlining the clinical relevance of our results. IMPLICATIONS: Our work emphasizes the key role of adjacent PPAT in prostate cancer dissemination and proposes new molecular targets for the treatment of obese patients exhibiting aggressive diseases.
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Tejido Adiposo/fisiopatología , Obesidad/complicaciones , Neoplasias de la Próstata/etiología , Animales , Técnicas de Cultivo de Célula , Humanos , Masculino , Ratones , Estrés Oxidativo , Neoplasias de la Próstata/patología , TransfecciónRESUMEN
Using qualitative data from 21 group discussions and unique survey data from a representative cross-section of 439 women in the Gaza Strip, we investigate how the Israeli military operation "Protective Edge" in 2014 influenced domestic violence (DV), accounting for risk factors at different levels of the ecological model. We combine our survey data with secondary data on infrastructure destruction across Gaza's neighborhoods, and use propensity score matching techniques to address endogeneity concerns. Our results show that the military operation increased DV, and that this effect manifests itself at relatively low-levels of destruction. Our analysis suggests that the mechanisms are displacement, a lowered ability of married women to contribute to household decision-making, and reduced social support networks.
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Desastres/estadística & datos numéricos , Violencia Doméstica/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Israel , Medio Oriente/etnología , Investigación Cualitativa , Factores de Riesgo , Estrés Psicológico/complicaciones , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Guerra/psicología , Guerra/estadística & datos numéricosRESUMEN
Cancer cells must adapt their metabolism in order to meet the energy requirements for cell proliferation, survival in nutrient-deprived environments, and dissemination. In particular, FA metabolism is emerging as a critical process for tumors. FA metabolism can be modulated through intrinsic changes in gene expression or signaling between tumor cells and also in response to signals from the surrounding microenvironment. Among these signals, extracellular vesicles (EVs) could play an important role in FA metabolism remodeling. In this review, we will present the role of EVs in tumor progression and especially in metabolic reprogramming. Particular attention will be granted to adipocytes. These cells, which are specialized in storing and releasing FAs, are able to shift tumor metabolism toward the use of FAs and, subsequently, increase tumor aggressiveness. Recent work demonstrates the involvement of EVs in this metabolic symbiosis.