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      Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models

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          Abstract

          Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is difficult to implement and maintain outside of the clinic. In this study, we aim to test a time-restricted feeding (TRF) approach on mouse models of obesity-driven postmenopausal breast cancer. We show that TRF abrogates the obesity-enhanced mammary tumor growth in two orthotopic models in the absence of calorie restriction or weight loss. TRF also reduces breast cancer metastasis to the lung. Furthermore, TRF delays tumor initiation in a transgenic model of mammary tumorigenesis prior to the onset of obesity. Notably, TRF increases whole-body insulin sensitivity, reduces hyperinsulinemia, restores diurnal gene expression rhythms in the tumor, and attenuates tumor growth and insulin signaling. Importantly, inhibition of insulin secretion with diazoxide mimics TRF whereas artificial elevation of insulin through insulin pumps implantation reverses the effect of TRF, suggesting that TRF acts through modulating hyperinsulinemia. Our data suggest that TRF is likely to be effective in breast cancer prevention and therapy.

          Abstract

          Obesity and its associated metabolic changes, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Here, the authors show that restricting when mice eat, but not what or how much they eat, delays breast cancer initiation and reduces tumor growth in obese mice in addition to improving insulin sensitivity and restoring circadian rhythms.

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          NIH Image to ImageJ: 25 years of image analysis

          For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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            Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.

            Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths). © 2014 UICC.
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              The insulin and insulin-like growth factor receptor family in neoplasia: an update.

              Although several early phase clinical trials raised enthusiasm for the use of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, initial Phase III results in unselected patients have been disappointing. Further clinical studies may benefit from the use of predictive biomarkers to identify probable responders, the use of rational combination therapies and the consideration of alternative targeting strategies, such as ligand-specific antibodies and receptor-specific tyrosine kinase inhibitors. Targeting insulin and IGF signalling also needs to be considered in the broader context of the pathophysiology that relates obesity and diabetes to neoplasia, and the effects of anti-diabetic drugs, including metformin, on cancer risk and prognosis. The insulin and IGFI receptor family is also relevant to the development of PI3K-AKT pathway inhibitors.
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                Author and article information

                Contributors
                nwebster@health.ucsd.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                25 January 2021
                25 January 2021
                2021
                : 12
                Affiliations
                [1 ]GRID grid.410371.0, ISNI 0000 0004 0419 2708, VA San Diego Healthcare System, ; San Diego, CA USA
                [2 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Medicine, Division of Endocrinology and Metabolism, , University of California San Diego, ; La Jolla, CA USA
                [3 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Pathology, , University of California San Diego, ; La Jolla, CA USA
                [4 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Moores Cancer Center, , University of California, San Diego, ; La Jolla, CA USA
                [5 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Radiology, , University of California, San Diego, ; La Jolla, CA USA
                [6 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Family Medicine and Public Health, Division of Preventive Medicine, , University of California San Diego, ; La Jolla, CA USA
                [7 ]GRID grid.215654.1, ISNI 0000 0001 2151 2636, College of Health Solutions, , Arizona State University, ; Phoenix, AZ USA
                Article
                20743
                10.1038/s41467-020-20743-7
                7835248
                33495474
                aec0cf64-6432-4406-903c-37e73400fe84
                © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may applyor(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                © The Author(s) 2021

                Uncategorized
                cancer,breast cancer,endocrine system and metabolic diseases
                Uncategorized
                cancer, breast cancer, endocrine system and metabolic diseases

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