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      The Use of 1α,25-Dihydroxyvitamin D 3 as an Anticancer Agent

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          Abstract

          The notion that vitamin D can influence the incidence of cancer arose from epidemiological studies. The major source of vitamin D in the organism is skin production upon exposure to ultra violet-B. The very first observation of an inverse correlation between exposure of individuals to the sun and the likelihood of cancer was reported as early as 1941. In 1980, Garland and Garland hypothesised, from findings from epidemiological studies of patients in the US with colon cancer, that vitamin D produced in response to sun exposure is protective against cancer as opposed to sunlight per se. Later studies revealed inverse correlations between sun exposure and the occurrence of prostate and breast cancers. These observations prompted laboratory investigation of whether or not vitamin D had an effect on cancer cells. Vitamin D is not active against cancer cells, but the most active metabolite 1α,25-dihydroxyvitamin D 3 (1,25D) has profound biological effects. Here, we review the anticancer action of 1,25D, clinical trials of 1,25D to date and the prospects of the future therapeutic use of new and low calcaemic analogues.

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          Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity.

          Longevity and aging are two sides of the same coin, as they both derive from the interaction between genetic and environmental factors. Aging is a complex, dynamic biological process characterized by continuous remodeling. One of the most recent theories on aging focuses on immune response, and takes into consideration the activation of subclinical, chronic low-grade inflammation which occurs with aging, named "inflammaging". Long-lived people, especially centenarians, seem to cope with chronic subclinical inflammation through an anti-inflammatory response, called therefore "anti-inflammaging". In the present review, we have focused our attention on the contrast between inflammaging and anti-inflammaging systems, by evaluating the role of cytokines and their impact on extreme longevity. Cytokines are the expression of a network involving genes, polymorphisms and environment, and are involved both in inflammation and anti-inflammation. We have described the role of IL-1, IL-2, IL-6, IL-12, IL-15, IL-18, IL-22, IL-23, TNF-α, IFN-γ as pro-inflammatory cytokines, of IL-1Ra, IL-4, IL-10, TGF-β1 as anti-inflammatory cytokines, and of lipoxin A4 and heat shock proteins as mediators of cytokines. We believe that if inflammaging is a key to understand aging, anti-inflammaging may be one of the secrets of longevity.
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            Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma.

            Epidemiological studies have suggested a reduced risk of several cancers associated with high vitamin D status. We performed a systematic review with meta-analyses of observational studies of serum 25-hydroxyvitamin D level and colorectal, breast and prostate cancer and colonic adenoma. The literature of December 2009 was searched without language restriction. The meta-regression analysis was done to compute dose-response effects. Because in case-control studies, serum 25-hydroxyvitamin D level is measured after the diagnosis of cancer, separate analyses for case-control and prospective studies were done. We identified 35 independent studies. The seven studies on colorectal adenomas were heterogeneous in terms of endpoint and control for major confounding factors, and we did not perform a meta-analysis of these data. The summary relative risk (SRR) and (95% confidence interval) for a 10 ng/ml increase in serum 25-hydroxyvitamin D was 0.85 (0.79; 0.91) for colorectal cancer (2,630 cases in 9 studies); 0.89 (0.81;0.98) for breast cancer (6,175 cases in 10 studies); and 0.99 (0.95;1.03) for prostate cancer (3,956 cases in 11 studies). For breast cancer, case-control studies (3,030 cases) had major limitations and obtained SRR of 0.83 (0.79; 0.87) whereas SRR of prospective studies (3,145 cases) was 0.97 (0.92; 1.03). For colorectal and breast cancer, differences between cases and controls in the season of blood draw or in overweight/obesity or physical inactivity could not explain the results. In conclusion, a consistent inverse relationship between serum 25-hydroxyvitamin D levels and colorectal cancer was found. No association was found for breast and prostate cancer. Copyright © 2010 UICC.
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              Inflammaging as a major characteristic of old people: can it be prevented or cured?

              Widespread aging at the population level is a recent phenomenon that emerged in affluent societies. Inflammation is necessary to cope with damaging agents and is crucial for survival, particularly to cope with acute inflammation during our reproductive years. But chronic exposure to a variety of antigens, especially to some viruses such as cytomegalovirus, for a period much longer than that predicted by evolution, induces a chronic low-grade inflammatory status that contributes to age-associated morbidity and mortality. This condition carries the proposed name "inflammaging". Centenarians are unique in that, despite high levels of pro-inflammatory markers, they also exhibit anti-inflammatory markers that may delay disease onset. The key to successful aging and longevity is to decrease chronic inflammation without compromising an acute response when exposed to pathogens.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                13 May 2016
                May 2016
                : 17
                : 5
                : 729
                Affiliations
                [1 ]Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland; ema@ 123456cs.uni.wroc.pl
                [2 ]Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; g.r.wallace@ 123456bham.ac.uk
                [3 ]Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
                Author notes
                [* ]Correspondence: g.brown@ 123456bham.ac.uk ; Tel.: +44-0121-414-4082
                Article
                ijms-17-00729
                10.3390/ijms17050729
                4881551
                27187375
                101fe788-e231-4e66-9eb7-b2b1aca02b36
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 March 2016
                : 10 May 2016
                Categories
                Review

                Molecular biology
                cancer,1α,25-dihydroxyvitamin d,analogues
                Molecular biology
                cancer, 1α,25-dihydroxyvitamin d, analogues

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