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      Trial watch: dietary interventions for cancer therapy

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          ABSTRACT

          Dietary interventions have a profound impact on whole body metabolism, including oncometabolism (the metabolic features allowing cancer cells to proliferate) and immunometabolism (the catabolic and anabolic reactions that regulate immune responses). Recent preclinical studies demonstrated that multiple dietary changes can improve anticancer immunosurveillance of chemo-, radio- and immunotherapy. These findings have fostered the design of clinical trials evaluating the capacity of dietary interventions to synergize with treatment and hence limit tumor progression. Here, we discuss the scientific rationale for harnessing dietary interventions to improve the efficacy of anticancer therapy and present up-to-date information on clinical trials currently investigating this possibility.

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants

            Summary Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m2 [underweight], 18·5 kg/m2 to <20 kg/m2, 20 kg/m2 to <25 kg/m2, 25 kg/m2 to <30 kg/m2, 30 kg/m2 to <35 kg/m2, 35 kg/m2 to <40 kg/m2, ≥40 kg/m2 [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. Findings We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m2 (95% credible interval 21·3–22·1) in 1975 to 24·2 kg/m2 (24·0–24·4) in 2014 in men, and from 22·1 kg/m2 (21·7–22·5) in 1975 to 24·4 kg/m2 (24·2–24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m2 in central Africa and south Asia to 29·2 kg/m2 (28·6–29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m2 (21·4–22·3) in south Asia to 32·2 kg/m2 (31·5–32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5–17·4) to 8·8% (7·4–10·3) in men and from 14·6% (11·6–17·9) to 9·7% (8·3–11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8–29·2) in men and 24·0% (18·9–29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4–4·1) in 1975 to 10·8% (9·7–12·0) in 2014 in men, and from 6·4% (5·1–7·8) to 14·9% (13·6–16·1) in women. 2·3% (2·0–2·7) of the world’s men and 5·0% (4·4–5·6) of women were severely obese (ie, have BMI ≥35 kg/m2). Globally, prevalence of morbid obesity was 0·64% (0·46–0·86) in men and 1·6% (1·3–1·9) in women. Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world’s poorest regions, especially in south Asia. Funding Wellcome Trust, Grand Challenges Canada.
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              Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study

              The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.
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                Author and article information

                Journal
                Oncoimmunology
                Oncoimmunology
                KONI
                koni20
                Oncoimmunology
                Taylor & Francis
                2162-4011
                2162-402X
                2019
                3 April 2019
                3 April 2019
                : 8
                : 7
                : 1591878
                Affiliations
                [a ]Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris, France
                [b ]INSERM, U1138 , Paris, France
                [c ]Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus , Villejuif, France
                [d ]Université Paris-Saclay , Orsay, France
                [e ]Fondation pour la Recherche Médicale , Paris, France
                [f ]Université Paris Descartes/Paris V, Sorbonne Paris Cité , Paris, France
                [g ]Université Pierre et Marie Curie/Paris VI , Paris, France
                [h ]INSERM U1015 , Villejuif, France
                [i ]CICBT507 , Villejuif, France
                [j ]Department of Radiation Oncology, Weill Cornell Medical College , New York, NY, USA
                [k ]Sandra and Edward Meyer Cancer Center , New York, NY, USA
                [l ]Department of Dermatology, Yale School of Medicine , New Haven, CT, USA
                [m ]Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP , Paris, France
                [n ]Department of Women’s and Children’s Health, Karolinska University Hospital , Stockholm, Sweden
                Author notes
                CONTACT Guido Kroemer kroemer@ 123456orange.fr ; Laurence Zitvogel laurence.zitvogel@ 123456orange.fr Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris, France
                Author information
                http://orcid.org/0000-0003-1596-0998
                http://orcid.org/0000-0002-9334-4405
                Article
                1591878
                10.1080/2162402X.2019.1591878
                6527263
                31143510
                d1adccdd-ffaa-4029-855c-190988c4c2da
                © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                History
                : 28 February 2019
                : 5 March 2019
                Page count
                Tables: 1, References: 93, Pages: 8
                Funding
                Funded by: Agence Nationale de la Recherche 10.13039/501100001665
                Award ID: E-Rare-2
                Funded by: Fondation pour la Recherche Médicale 10.13039/501100002915
                Award ID: FRM FDT201805005722
                Funded by: H2020 European Research Council 10.13039/100010663
                Award ID: Oncobiome
                This work was supported by the Agence Nationale de la Recherche [E-Rare-2]; Fondation pour la Recherche Médicale [FRM FDT201805005722]; H2020 European Union [Oncobiome].
                Categories
                Review

                Immunology
                alternate-day fasting,caloric restriction mimetics,chemotherapy,fasting-mimicking diet,immune checkpoint blockers,ketone bodies

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