Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa

Holt, Peter R.; Bresalier, Robert S.; Chan, Kevin M.; Liu, Kai-Feng; Lipkin, Martin; Byrd, James C.; Yang, Kan

doi:10.1002/cncr.21618

Cited by 54 publications

(33 citation statements)

References 35 publications

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“…At the molecular level, Holt et al (2006) showed that combined daily supplementation of 11 patients with vitamin D 3 (400 IU) and calcium (1.5 g) for 6 months reduced the proliferation of colonic flat mucosa and polyps, and increased the expression of BAK1 and diminished that of the CRC-associated mucin MUC5AC in the polyps when compared with the placebo group (8 patients). In a series of recent papers, Fedirko et al reported that 800 IU/day vitamin D 3 and/or 2 g/day calcium (in 92 patients with at least one adenoma, 6 months treatment) increased BAX and p21 CIP1 expression in colorectal crypts (Fedirko et al 2009a,b).…”

Section: Anti-tumoural Action Of Vitamin D In Animal Models Of Crcmentioning

confidence: 99%

Vitamin D and colon cancer

Перейра¹,

Larriba²,

Múñoz³

2012

Endocrine-Related Cancer

104

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The most active vitamin D metabolite, 1α,25-dihydroxyvitamin D3(1,25(OH)2D3), is a pleiotropic hormone with wide regulatory actions. Classically, vitamin D deficiency was known to alter calcium and phosphate metabolism and bone biology. In addition, recent epidemiological and experimental studies support the association of vitamin D deficiency with a large variety of human diseases, and particularly with the high risk of colorectal cancer. By regulating the expression of many genes via several mechanisms, 1,25(OH)2D3induces differentiation, controls the detoxification metabolism and cell phenotype, sensitises cells to apoptosis and inhibits the proliferation of cultured human colon carcinoma cells. Consistently, 1,25(OH)2D3and several of its analogues decrease intestinal tumourigenesis in animal models. Molecular, genetic and clinical data in humans are scarce but they suggest that vitamin D is protective against colon cancer. Clearly, the available evidence warrants new, well-designed, large-scale trials to clarify the role of vitamin D in the prevention and/or therapy of this important neoplasia.

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Section: Anti-tumoural Action Of Vitamin D In Animal Models Of Crcmentioning

confidence: 99%

Vitamin D and colon cancer

Перейра¹,

Larriba²,

Múñoz³

2012

Endocrine-Related Cancer

104

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“…While numerous mechanisms have been implicated, reversal of the colonic epithelial hyperproliferation appears to be of major importance. Indeed, there is strong evidence that for many agents, proliferation in the uninvolved mucosa tends to be a reliable intermediate biomarker for chemoprevention (3,(6)(7)(8)(9). Unfortunately, none of the well-established anti-proliferative agents could be exploited in long-term clinical practice mainly over concerns of marginal efficacy (calcium, folate, fiber) and above all toxicity (higher gastrointestinal or cardiovascular toxicity for NSAIDs) (10,11).…”

Section: Introductionmentioning

confidence: 99%

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

Roy

Koetsier²,

Tiwari³

et al. 2011

Int J Oncol

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Abstract. Polyethylene glycol (PEG) is a safe and effective chemopreventive agent against colorectal carcinogenesis in cell culture, animal models and human subjects. Although the precise molecular mechanism is unclear, we previously reported that PEG suppresses colonic epithelial proliferation. As cellular proliferation is driven by complex G1-S phase transition, we now characterize the role of PEG on cell cycle regulation. We focused our attention on the effect of PEG on the CDK inhibitor p21 cip1/waf1 , which is implicated in early colon carcinogenesis and is upregulated by non-steroidal anti-inflammatory drugs. These studies were done in the azoxymethane-treated (AOM) rat model as well as in HT-29 colon cancer cells. Immunohistochemical analysis revealed that while AOM decreased the p21 expression (75%, p<0.01) in the premalignant colonic mucosa, PEG induced p21 levels back to normal. These findings paralleled a decreased BrdUrd incorporation (78%, p<0.001) and hypophosphorylated retinoblastoma protein (Rb; by 47%) signifying PEG's antiproliferative activity. Furthermore, in HT-29 cells, PEG decreased proliferation as measured by PCNA (68% reduction), increased p21 expression (2.3-fold), induced cell cycle arrest during G0/G1 phase (45% reduction in S phase cells) and inhibited the phosphorylation of Rb (by 52% compared to untreated). PEG caused greater than a 2-fold induction of protein and mRNA level of p21 cip1/waf1 in HT-29 cells. These results demonstrate for the first time that PEG is involved in p21 regulation concomitant with G1➝S phase cell cycle arrest and it is through these effects that it can exert its anti-proliferative and hence chemopreventive role.

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“…Two small RCTs examined the effects of calcium plus vitamin D on the epithelial cell proliferation from colorectal mucosa and polyps (Holt et al, 2002(Holt et al, , 2006 …”

Section: Vitamin D As a Research Intervention In Randomized Controllmentioning

confidence: 99%

“…It has been shown that vitamin D increases the apoptosis in the colorectal epithelium, thereby reducing the risk of developing colorectal neoplasia (Holt et al, 2002(Holt et al, , 2006. Indeed, many cell types, including colorectal epithelial cells, contain vitamin D receptors (VDRs) and express 1-a-hydroxylase.…”

mentioning

confidence: 99%

One Disease, Two Lives

Visco

Meyer²,

Xi³

et al. 2009

Clinical Journal of Oncology Nursing

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Vitamin D deficiency is common in the general public and in patients with cancer. Optimizing vitamin D intake is increasingly recognized in cancer risk reduction, particularly in decreasing colorectal cancer risk. Therefore, summarizing the current evidence to promote best practices related to vitamin D intake and colorectal cancer risk reduction is important. The objectives of this article are to examine the current evidence regarding the impact of vitamin D on colorectal cancer risk reduction and provide practice recommendations for clinicians. Relevant research articles from 2002-2008 were retrieved from multiple electronic databases. Reference lists of relevant articles also were searched manually. Twenty-five research reports were selected for this article: 4 randomized, controlled trials; 11 cohort or case-control studies measuring serum 25-OH-D levels; and 10 cohort studies reporting vitamin D intake. This review generated three themes: raising 25-OH-D levels to a vitamin D sufficient state (32-100 ng/ml) achieved colorectal cancer risk reduction, increasing the intake of vitamin D reduced colorectal cancer risk, and increasing vitamin D intake to 1,000 IU daily is safe and likely sufficient to raise serum 25-OH-D levels above 32 ng/ml to achieve colorectal cancer risk reduction. Several practice recommendations are suggested. Journal Club ArticleOptimizing Vitamin D Status to Reduce Colorectal Cancer Risk:An Evidentiary Review At a GlanceVitamin D deficiency or insufficiency (less than 32 ng/ml or 80  nmol/L) is common in the general population and in patients with cancer.Current evidence suggests that optimizing serum 25-OH-D  levels to the normal range of 32-100 ng/ml is associated with colorectal cancer risk reduction.Daily vitamin D intake of 1,000 IU is safe and likely sufficient  to reduce colorectal cancer risk.

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Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa

Cited by 54 publications

References 35 publications

Vitamin D and colon cancer

Vitamin D and colon cancer

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

One Disease, Two Lives

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