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"Retinol-induced Intestinal Tumorigenesis in Min/+ Mice and Importance of Vitamin D Status. Hetland RB, Alexander J, Berg JP, Svendsen C, Paulsen JE. Anticancer Res. 2009 Nov;29(11):4353-60. PMID: 20032378 The effects of life-long dietary exposure, starting in utero, to high retinol, low vitamin D, or high retinol in combination with low vitamin D on intestinal tumorigenesis in Min/+ mice were investigated. In males, high retinol alone significantly increased the number (2.6-fold) and size (1.3-fold) of small intestinal tumours; in females no significant increase in tumour number or size was seen. In both genders, low vitamin D intake alone did not affect intestinal tumorigenesis. In males, intake of the combined high retinol/low vitamin D diet did not further increase the effects caused by high retinol alone. In females, however, the high retinol/low vitamin D-induced increase in tumour number (3.1-fold) and tumour size (1.5-fold) exceeded that of high retinol alone. In conclusion, a high dietary intake of retinol stimulated intestinal tumorigenesis in Min/+ mice. Furthermore, the results indicate a combined effect of high retinol and low vitamin D on tumorigenesis in females"

Vitamin D-induced up-regulation of tumour necrosis factor alpha (TNF-alpha) in prostate cancer cells. Golovko O, Nazarova N, Tuohimaa P. Life Sci. 2005 Jun 17;77(5):562-77. Epub 2005 Feb 25. PMID: 15904673 doi:10.1016/j.lfs.2004.10.072 Combined addition of human recombinant TNF-alpha with calcitriol or CB1093 cause enhanced effect in induction of apoptosis. We conclude that under physiological conditions vitamin D activates only the transcription of TNF-alpha gene, for TNF-alpha protein synthesis additional cofactors are required. Therefore a cooperation of vitamin D and TNF-alpha may play an important role in the control of cell growth in prostate cancer.

"Vitamin D-dependent calcium binding proteins were discovered in the cytosolic fractions of chicken intestine, and later in mammalian intestine and kidney, by workers including Robert Wasserman of Cornell University. They bound calcium in the micromolar range and were greatly reduced in vitamin D-deficient animals. Expression could be induced by treating these animals with vitamin D metabolites such as calcitriol. They were found to exist in two distant sizes with a molecular weight of approximately 9 kDa and 28 kDa. They were renamed calbindin; calbindin-D9k is found in mammalian intestine and calbindin-D28k in avain intestine and in kidney."

'Vitamin D Induces Innate Antibacterial Responses in Human Trophoblasts via an Intracrine Pathway.\nLiu N, Kaplan AT, Low J, Nguyen L, Liu GY, Equils O, Hewison M.\nBiol Reprod. 2009 Mar;80(3):398-406. Epub 2008 Nov 12.\nPMID: 19005165DOI: 10.1095/biolreprod.108.073577

MedWire News: Calcitriol, the active form of vitamin D, has been found to induce the tumor-suppressing protein CCAAT enhancer-binding protein (C/EBP)α, which can inhibit the growth of breast cancer cells, researchers report.

SSeason of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Porojnicu AC, Robsahm TE, Ree AH, Moan J. Br J Cancer. 2005 Sep 5;93(5):571-4. PMID: 16136030 doi:10.1038/sj.bjc.6602722 Epidemiological data for this period indicate that season of diagnosis is a strong prognostic factor for Hodgkin's lymphoma, with approximately 20% lower case fatality for patients diagnosed during autumn vs winter diagnosis (RR = 0.783, 95% CI,-0.62 to 0.99; P = 0.041). Notably, the improved autumnal survival rate was higher than 60% (RR = 0.364, 95% CI, -0.15 to 0.87; P = 0.025) for patients younger than 30 years. This finding may be related to higher endogenous levels of vitamin D in autumn, with a favourable influence on the conventional therapy. In conclusion, we have found that the prognosis of Hodgkin's lymphoma is significantly correlated with the season of diagnosis, particularly for patients younger than 30 years. This seasonal effect is presumably due to the vitamin D3 synthesis in skin during sun exposure. The present findings should encourage further investigations of the possible adjuvant role of vitamin D derivatives in cancer therapy

A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Acid-base balance has an effect on bone turnover, especially on the rates of bone resorption and calcium mobilization. Bone mineral participates in the defense against acid-base disturbances, especially against metabolic acidosis (Lemann et al. 1966, Green & Kleeman 1991). The role of the bone mineral is important in the acid-base disorders, as no appreciable change in the intestinal calcium absorption occurs (Bichara et al. 1990). In the mammalian body, mainly three hormones regulate the calcium metabolism and the bone turnover. 1,25-dihydroxycholecalciferol (vitamin D derivative) increases calcium absorption from the intestine and, indirectly, from bone. Parathyroid hormone mobilizes calcium from the bone and increases the urinary phosphate excretion. Calcitonin inhibits bone resorption (Ganong 1981). Used as drugs, these hormones are also capable of inducing acid-base disorders. Calcitonin administration (Escanero et al. 1991) and vitamin D excess (Bichara et al. 1990) have been reported to cause metabolic alkalosis.

Vitamin D: the alternative hypothesis. Albert PJ, Proal AD, Marshall TG. Autoimmun Rev. 2009 Jul;8(8):639-44. Epub 2009 Feb 12. Review. PMID: 19393200 Emerging molecular evidence suggests that symptomatic improvements among those administered vitamin D is the result of 25-D's ability to temper bacterial-induced inflammation by slowing VDR activity. While this results in short-term palliation, persistent pathogens that may influence disease progression, proliferate over the long-term.

Low vitamin D status, high bone turnover, and bone fractures in centenarians. Passeri G, Pini G, Troiano L, Vescovini R, Sansoni P, Passeri M, Gueresi P, Delsignore R, Pedrazzoni M, Franceschi C. J Clin Endocrinol Metab. 2003 Nov;88(11):5109-15. PMID: 14602735 We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.

The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Gombart AF. Future Microbiol. 2009 Nov;4:1151-65. PMID: 19895218 Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications

"If you're running low on vitamin D - as an estimated 70 percent of the U.S. population is - your immune system may not be functioning as well as it should. As a result, you may be more vulnerable to infectious diseases than you would if your vitamin D levels were optimal. Worse, you could be at higher than normal risk of a long list of diseases including heart disease and several kinds of cancer. A report recently published journal, Future Microbiology, highlighted research at the Linus Pauling Institute at Oregon State University, which has shown that vitamin D induces expression of an antimicrobial peptide gene called cathelicidin that is the "first line of defense" in the immune system's response to minor wounds, cuts and bacterial and viral infections. The regulation of cathelicidin by vitamin D could help explain its vital role in immune function. The report noted that vitamin D is a key cofactor in reducing inflammation, in blood pressure control and helping to protect against heart disease. Author Adrian Gombart explains that there is still much to explore about D's mechanisms of action, the potential use of synthetic analogs of it in new treatments, and its duty in fighting infection."

Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. Jiang F, Bao J, Li P, Nicosia SV, Bai W. J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12. PMID: 15485861 doi: 10.1074/jbc.M410395200 Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression. Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene. It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro