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Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells. Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element–binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody. Results: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter. Conclusions: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells. METHODS: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element-binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT- qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti- SREBP antibody. RESULTS: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter. CONCLUSIONS: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer. [ABSTRACT FROM AUTHOR]

Criminal activities are often unevenly distributed over space. The literature shows that the occurrence of crime is frequently concentrated in particular neighbourhoods and is related to a variety of socioeconomic and crime opportunity factors. This study explores the broad patterning of property and violent crime among different socio-economic stratums and across space by examining the neighbourhood socioeconomic conditions and individual characteristics of offenders associated with crime in the city of Toronto, which consists of 140 neighbourhoods. Despite being the largest urban centre in Canada, with a fast-growing population, Toronto is under-studied in crime analysis from a spatial perspective. In this study, both property and violent crime data sets from the years 2014 to 2016 and census-based Ontario-Marginalisation index are analysed using spatial and quantitative methods. Spatial techniques such as Local Moran's I are applied to analyse the spatial distribution of criminal activity while accounting for spatial autocorrelation. Distance-to-crime is measured to explore the spatial behaviour of criminal activity. Ordinary Least Squares (OLS) linear regression is conducted to explore the ways in which individual and neighbourhood demographic characteristics relate to crime rates at the neighbourhood level. Geographically Weighted Regression (GWR) is used to further our understanding of the spatially varying relationships between crime and the independent variables included in the OLS model. Property and violent crime across the three years of the study show a similar distribution of significant crime hot spots in the core, northwest, and east end of the city. The OLS model indicates offender-related demographics (i.e., age, marital status) to be a significant predictor of both types of crime, but in different ways. Neighbourhood contextual variables are measured by the four dimensions of the Ontario-Marginalisation Index. They are significantly associated with violent and property crime in different ways. The GWR is a more suitable model to explain the variations in observed property crime rates across different neighbourhoods. It also identifies spatial non-stationarity in relationships. The study provides implications for crime prevention and security through an enhanced understanding of crime patterns and factors. It points to the need for safe neighbourhoods, to be built not only by the law enforcement sector but by a wide range of social and economic sectors and services. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells., Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element-binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody., Results: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter., Conclusions: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)