ABSTRACT؉ clonogenic myeloid cells was unaltered by short exposures to hypoxia. In contrast, the chondrogenic differentiation potential of BMMCs was enhanced by hypoxia, whereas adipogenesis and osteogenesis were unaltered. When their transcriptional profiles were compared, 183 genes in UCB CD133 ؉ cells and 45 genes in BMMC were differentially regulated by hypoxia. These genes included known hypoxia-responsive targets such as BNIP3, PGK1, ENO2, and VEGFA, and other genes not previously described to be regulated by hypoxia. Several of these genes, namely CDTSPL, CCL20, LSP1, NEDD9, TMEM45A, EDG-1, and EPHA3 were confirmed to be regulated by hypoxia using quantitative reverse transcriptase polymerase chain reaction. These results, therefore, provide a global view of the signaling and regulatory network that controls oxygen sensing in human adult stem/progenitor cells derived from hematopoietic tissues.

The metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (also known as calcitriol), is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D3 signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol) in modulating cellular growth and development. Vitamin D (calcitriol) acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.

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Global cancer incidence and mortality rates are high and increasing. Thus, it is imperative to find novel solutions to preventing cancer incidence and treating it at an affordable yet efficacious manner. The solar UVB-vitamin D-cancer hypothesis was first proposed in 1980 based on a geographical ecological study. Since then, numerous ecological and observational studies as well as studies of mechanisms have provided support for the hypothesis. However, observational studies have not provided consistent support, in part due to using a single blood draw from any season to use for serum 25-hydroxyvitamin D [25(OH)D] concentration in prospective studies with long follow-up times. Case-controls studies, in which blood is drawn near time of diagnosis, and prospective studies in which blood is drawn in the sunnier half of the year, are more likely to find significant inverse relations between 25(OH)D and cancer incidence. Three vitamin D plus calcium clinical trials have found significant reduction in all-cancer incidence. This paper reviews the evidence for vitamin D in reducing incidence of and increasing survival from breast, colorectal, lung, ovarian, pancreatic, and prostate cancer. The epidemiological evidence provides strong support for all of these types of cancer except for non-aggressive prostate cancer. Studies of the cellular mechanisms of vitamin D action in different cancer cell types, strongly indicate that vitamin D can exert protective and anti-tumorigenic activities that would retard cellular transformation, hyperplasia and cancer progression. Based on the scientific evidence reviewed in this paper, individuals and health providers can consider increasing 25(OH)D concentrations through sensible sun exposure and/or vitamin D supplementation to reduce risk of and, in conjunction with standard care, treat cancer. Public health acceptance of vitamin D for cancer prevention and treatment requires stronger support from vitamin D clinical trials.

The global death toll from noncommunicable diseases is exceptionally high, reported to cause 71% of global deaths worldwide. Metabolic syndrome risk factors, especially excessive adiposity and obesity, are at the heart of the problem resulting in increased co-morbidities such as cardiometabolic diseases and cancer, increased health costs, poorer quality of life, and shortened survival. Vitamin D 3 can positively reverse many of these adverse effects and outcomes through blocking signaling mechanisms that predispose to cardiometabolic and metastatic disease. As an affordable natural agent, vitamin D 3 can be used to counteract obesity-induced inflammation, block early adipogenesis, enhance glucose uptake, counteract hyperleptinemia, ameliorate insulin resistance, and reduce hypertension. This is supported by data from in vitro, in vivo and epidemiological studies and clinical trials. We propose that everyone in general and obese patients in particular consider raising 25-hydroxyvitamin D levels through UVB exposure and/or supplemental vitamin D 3 intake to reduce cardiometabolic and metastatic disease and increase longevity.