Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer.

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)-dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity.

Gender differential in inclination to donate brain for research among Nigerians: the IBADAN Brain Bank Project.

BACKGROUND: Laboratory-based studies of neurological disease patterns and mechanisms are sparse in sub-Saharan Africa. However, availability of human brain tissue resource depends on willingness towards brain donation. This study evaluated the level of willingness among outpatient clinic attendees in a Nigerian teaching hospital. METHODS: Under the auspices of the IBADAN Brain Bank Project, a 43-item semi-structured interviewer-administered questionnaire was designed to evaluate knowledge, attitude, and beliefs of individuals attending Neurology, Psychiatry and Geriatrics Outpatient clinics regarding willingness to donate brain for research. Association between participants characteristics and willingness towards brain donation was investigated using logistic regression models. Analysis was conducted using Stata SE version 12.0. RESULTS: A total of 412 participants were interviewed. Their mean age was 46.3 (16.1) years. 229 (55.6%) were females and 92.5% had at least 6 years of formal education. Overall, 109 (26.7%) were willing to donate brains for research. In analyses adjusting for educational status, religion, ethnicity, marital status and family setting, male sex showed independent association with willingness towards brain donation OR (95% CI) 1.7 (1.08-2.69), p = 0.023. Participants suggested public engagement and education through mass media (including social media) and involvement of religious and community leaders as important interventions to improve awareness and willingness towards brain donation. CONCLUSION: The survey revealed low willingness among outpatient clinic attendees to donate brain for research, although men were more inclined to donate. It is imperative to institute public engagement and educational interventions in order to improve consent for brain donation for research.

Brain banking in low and middle-income countries: Raison D'être for the Ibadan Brain Ageing, Dementia And Neurodegeneration (IBADAN) Brain Bank Project.

Brain banks are biorepositories of central nervous system (CNS) tissue including fixed and frozen whole brains, brain biopsies and spinal cord, as well as body fluids comprising the cerebrospinal fluid (CSF) and blood stored for research purposes. Though several independent brain banks exist in high income countries, only five low- and middle - income countries (LMIC) have brain banks. The African continent is yet to establish a formalized brain bank despite its huge human genomic diversity, ageing of her populations with concomitant increases in ageing - associated brain disorders and differential phenotypic expression and outcomes of brain disorders. Cellular and molecular clinicopathological studies are vital to shaping our understanding of the interaction between racial (genetic) and geographical (environmental) factors in the natural history and mechanisms of disease, and unravelling frameworks of diagnostic biomarkers, and new therapeutic and preventative interventions. The Ibadan Brain Ageing, Dementia And Neurodegeneration (IBADAN) Brain Bank, the first organized brain tissue biorepository in sub - Saharan Africa, is set up to accrue, process and store unique brain tissues for future research into a broad spectrum of neurological and psychiatric disorders. The potential unique discoveries and research breakthroughs will benefit people of African ancestry and other ancestral populations.

Mammographic breast pattern in Nigerian women in Ibadan, Nigeria.

INTRODUCTION: Mammographic breast density is dependent on the relative proportion of radiolucent fat and radio-dense connective and glandular tissue. This breast density is said to be a marker of risk for breast cancer and has received widespread interest in many countries in recent years. AIMS AND OBJECTIVES: The main objective of this study is to estimate the prevalence of the various mammographic breast density patterns and seeks to find any association between the reported breast patterns and various demographic variables in women in Ibadan, South West Nigeria. METHODS: A prospective descriptive study of mammographic breast pattern in 498 women at the Department of Radiology, University College Hospital Ibadan. Two screening views and additional views when necessary were done on each breast with the Senographe DMR+ Mammographic Unit. Participants also completed an assisted administered questionnaire which was used to obtain data on their socio-demographic characteristics. RESULTS: The study confirmed significant association with age and parity as in previous reports in the diaspora. CONCLUSION: The study confirmed denser mammographic breast pattern in younger and nulliparous women. Future work on mammographic density and other variables is contemplated for complete cancer related data in our peculiar setting.

Mammary cancer and social interactions: identifying multiple environments that regulate gene expression throughout the life span.

Now that the human genome has been sequenced, along with those of major animal models, there is an urgent need to define those environments that interact with genes. The traditional view focuses on ways that gene products interact with the nuclear environment to regulate cell function, causing the physiologic changes, behaviors, and diseases manifest throughout development and aging. Although this view is essential, it is equally essential to understand the converse relationship, namely, to identify those environments at higher levels of organization that regulate the expression of specific genes. Given the vastness of this problem, one effective strategy is to start with a trait for which some of the genes have already been identified, such as malignant disease. In rats, social isolation and hypervigilance increase the incidence of mammary tumors, accelerate aging, and shorten the life span. We propose that similar environmental regulation of gene expression may underlie the disproportionately high mortality from premenopausal breast cancer of Blacks, a minority group that can experience high levels of loneliness and hypervigilance. Our goal is to identify which environments-social, psychological, hormonal, and cellular-regulate genetic mechanisms of mammary cancer risk as well as the specific times in the life span when they do so.

Reducing disparities in breast cancer survival: a Columbia University and Avon Breast Cancer Research and Care Network Symposium.

On November 8th, 2001, faculty from Universities, government and non-profit community organizations met to determine how, separately and together, they could address disparities in survival of women with breast cancer in the diverse patient populations served by their institutions. Studies and initiatives directed at increasing access had to date met modest success. The day was divided into three sections, defining the issues, model programs, government initiatives and finally potential collaborations. By publishing these proceedings, interested readers will be aware of the ongoing programs and studies and can contact the investigators for more information. The Avon Foundation funded this symposium to bring together interested investigators to share programmatic experiences, data and innovative approaches to the problem.