The anti-cancer and anti-inflammatory actions of 1,25(OH)2D3

Vanoirbeek, Els; Krishnan, Aruna V.; Eelen, Guy; Verlinden, Lieve; Bouillon, Roger; Feldman, David; Verstuyf, Annemieke

doi:10.1016/j.beem.2011.05.001

Cited by 90 publications

(86 citation statements)

References 94 publications

(112 reference statements)

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“…[58] Several epidemiological studies have revealed a relationship between an individual's vitamin D status and the risk of developing cancer. [59] The VDR is essential to initiate the genomic and non-genomic signaling pathways that are induced by vitamin D, and has been shown to play a critical role in its anti-cancer activity. This is evidenced by multiple studies, which have reported that VDR expression is gradually reduced when the tumor disease stage advances, and by the existence of VDR gene polymorphisms that are associated with cancer risk.…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

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Section: Discussionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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“…Growing evidence indicates that Vit D may play an important role in the inhibition of tumor angiogenesis (Vanoirbeek et al, 2011;Xu et al, 2013). This peculiar function has been defined with the term ''angioprevention'' (Tosetti et al, 2002).…”

Section: Effects Of Vitamin D On Vascular Cells and Angiogenesismentioning

confidence: 99%

“…The induction of apoptosis is an additional, important mechanism by which Vit D appears to exert its chemopreventive effects on cancer cell growth (Vanoirbeek et al, 2011).…”

Section: Vit D and Apoptosismentioning

confidence: 99%

“…In this context, a consistent body of investigation provides evidence that Vitamin D (Vit D) and its metabolites, in addition to its well-known involvement in calcium homeostasis, also appears to be effective in preventing the malignant transformation and the progression of various types of human tumors (Krishnan & Feldman, 2010;Nagpal et al, 2005;Vuolo et al, 2012). On one hand, experimental evidence indicates that these effects appear to be likely due to the antiproliferative, proapoptotic, and immunomodulatory activities with which these molecules are endowed (Krishnan & Feldman, 2010;Vanoirbeek et al, 2011). On the other hand, numerous epidemiological observations based on geographic variation in the incidence of cancer and\or mortality in relation to 18 different types of human cancer clearly demonstrate that Vit D exerts chemopreventive effects on at least three types of solid tumors at high risk of mortality, namely breast cancer (Khan et al, 2010), prostate cancer (Swami et al, 2011), and colorectal cancer (Pereira et al, 2012) and on squamous cell carcinoma (SCC) and some hematological malignances (Kim et al, 2012;Reddy, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D in cancer chemoprevention

Giammanco¹,

Majo²,

Guardia

et al. 2015

Pharmaceutical Biology

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Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Results and conclusion: Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.

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“…7 However, it has numerous additional roles such as regulation of cellular proliferation, apoptosis, differentiation and inflammation. 8,9 Vitamin D generation is a multi-step process involving the skin, …”

Section: Introductionmentioning

confidence: 99%