Saturday, February 22, 2014

Vitamin D and Endometrial Cancer


Kyle J. Norton(Draft Article)
Epidemiological studies foscusing in the level of circulating 25-hydroxyvitamin D (25(OH)D and dietary vitamin D in reduced risk of endometrial cancer have been inconclusive.
The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.
Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain Vitamins, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.

Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.

 A nested case-control study, including 830 cases and 992 controls from 7 cohorts showed that there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index(1). The analysis of the effect of 25(OH)D and total dietary vitamin D intake used the Cox proportional hazards model, also indiacted no protection against the development of endometrial cancer with intake of vitamin D(1a) and  in an obese animal model, inhibited obesity-induced increase in endometrial lesions but not endometrial cancer risk(1b). But the study of The Cancer Registry of Norway, Institute of Population-based Cancer Research, indicated that a serum level of 25-OHD around 50 nmol/L appears to be a threshold level, lower serum levels of 25-OHD may be associated to cancer due to several mechanisms. including Vitamin D supplementation could retard the disease process or prolong survival time(2)(3). Other in the study of the effects of progesterone, calcitriol, and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells, showed a sgnificant increased levels of circulating 25-hydroxyvitamin D (25(OH)D and  inhibition of cell proliferation through caspase-3 activation and induction of G0-G1 cell-cycle arrest with associated downregulation of cyclins D1 and D3 and p27 induction(4). In the differentiation of serum 25-hydroxyvitamin D (25(OH)D) concentrations with incidence and/or mortality rates for about 20 types of cancer and improved survival rates for eight types of cancer, suggested that  both measurements of serum 25(OH)D concentrations and increasing serum 25(OH)D concentrations  should be considered of those diagnosed with cancer, of that may improved survival rates and reduced disparities(5). The expression of SEMA3B, SEMA3F(secreted proteins that regulate angiogenesis, tumor growth, and metastasis), are found to be lower in women with endometrial cancer, due tothe the loss of SEMAs in contribution to the malignant phenotype of endometrial cancer cells,  72 hours treatment with conbination of progesterone (P4) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]  showed a a significant upregulation of SEMA3B and SEMA3F and inhibited growth of cancer cells by increasing caspase-3 activity(6).

Taking altogether, without going into reviews, vitamin D and high levels of circulating 25-hydroxyvitamin D (25(OH)D may be associated to reduced risk and treatment of endometrial cancerthrough certain mechanisms such as cell cycle arrest, upregaulation induced apoptic and anti proliferative expessions. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.
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References
(1) Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers by Zeleniuch-Jacquotte A1, Gallicchio L, Hartmuller V, Helzlsouer KJ, McCullough ML, Setiawan VW, Shu XO, Weinstein SJ, Weiss JM, Arslan AA, De Vivo I, Gao YT, Hayes RB, Henderson BE, Horst RL, Koenig KL, Patel AV, Purdue MP, Snyder K, Steplowski E, Yu K, Zheng W, Hankinson SE.(PubMed)
(1a) Prospective analysis of vitamin D and endometrial cancer risk by Liu JJ1, Bertrand KA, Karageorgi S, Giovannucci E, Hankinson SE, Rosner B, Maxwell L, Rodriguez G, De Vivo I.(PubMed)
(1b) Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- mice by Yu W1, Cline M, Maxwell LG, Berrigan D, Rodriguez G, Warri A, Hilakivi-Clarke L.(Pubmed)
(2) The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation by Robsahm TE1, Schwartz GG, Tretli S.(PubMed)
(3) Seasonal vitamin D changes and the impact on health risk assessment by Rosecrans R1, Dohnal JC(PubMed)
(4) Progesterone enhances calcitriol antitumor activity by upregulating vitamin D receptor expression and promoting apoptosis in endometrial cancer cells by Lee LR1, Teng PN, Nguyen H, Hood BL, Kavandi L, Wang G, Turbov JM, Thaete LG, Hamilton CA, Maxwell GL, Rodriguez GC, Conrads TP, Syed V.(PubMed)
(5) Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and white Americans by Grant WB, Peiris AN.(PubMed)
(6) Progesterone and 1,25-dihydroxyvitamin D₃ inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F by Nguyen H1, Ivanova VS, Kavandi L, Rodriguez GC, Maxwell GL, Syed V.(PubMed)

Vitamin C and Endometrial Cancer

Epidemiological studies, linking vitamin C in reduced risk and treatment of endometrial cancer have been inclusive(1)(2).
Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.

The University of Otago, may have found a link of  Low ascorbate levels and activation of increased activation of the HIF-1 pathway to endometrial cancer.Women wgo were disgnosed with endometrial cancer with low levels of ascorbate were found to have a elevated VEGF(a signal protein produced by cells that stimulates vasculogenesis and angiogenesis), GLUT-1(Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels), and BNIP3(a potent inducer of autophagy in many cells) protein levels and with increased tumor size(3). Strong evidences also suggested that reactive oxygen species(ROS) are responsible for proteasome inhibitor-induced cell killing, vitamin C is found to  inhibit cell death through blocking the triggering proteasome inhibition(4). A combination including riboflavin, niacin and ascorbic acid, caused a significant decrease in the activity of glycolytic enzymes and a significant increase in the activities of gluconeogenic enzymes to near normal levels in experimental animals and may be considered as potential agent against tamoxifen mediated secondary endometrial carcinoma(5) and intake of vitamin C is associated to reduced risk of
endometrial cancer(6).
In secondary endometrial carcinoma bearing rat, the combination of  riboflavin, niacin and ascorbic acid exhibit their effects against tamoxifen mediated endometrial carcinoma, through a significant decrease in the activity of glycolytic enzymes(promoting continuous transport of glucose into the cell)(7). In a cultured human endometrial adenocarcinoma (AN3CA) cells, another combination of  application of sodium ascorbate (Vitamin C) and 2-methyl-1,4-naphthoquinone (Vitamin K3) stimulated cytotoxicity through the formation of reactive oxygen radicals, possibly accentuated by less defined secondary mechanisms(8). the syudy of the composition of ascorbic acid, pyruvic acid and the activity of malate dehydrogenase decarboxylizing (MDHD), also showed the increased reduced form of ascorbic and pyruvic acid in malignant growth(9).

Taking altogether, the combination of vitamin C and others may be associated to reduced risk and treatment of endometrial cancer through inhibition of cell cycle, and other mechanism such as decrease in the activity of glycolytic. Daily ingestion of high-dose vitamin C may be considered safe, but in rare incidence, overdoses in a prolonged period of time, may cause intra-renal oxalate crystal deposition, a fatal nephrotoxicity(10)(11).
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References
(1) Risk of endometrial cancer in relation to individual nutrients from diet and supplements by Biel RK1, Csizmadi I, Cook LS, Courneya KS, Magliocco AM, Friedenreich CM.(PubMed)
(2) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH1, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(3) Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer by Kuiper C1, Molenaar IG, Dachs GU, Currie MJ, Sykes PH, Vissers MC(PubMed))
(4) Antioxidants block proteasome inhibitor function in endometrial carcinoma cells by Llobet D1, Eritja N, Encinas M, Sorolla A, Yeramian A, Schoenenberger JA, Llombart-Cussac A, Marti RM, Matias-Guiu X, Dolcet X.(PubMed)
(5) Therapeutic potential of riboflavin, niacin and ascorbic acid on carbohydrate metabolizing enzymes in secondary endometrial carcinoma bearing rats by Sundravel S1, Shanthi P, Sachdanandam P.(PubMed)
(6) Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis.
Bandera EV1, Gifkins DM, Moore DF, McCullough ML, Kushi LH(PubMed)
(7) Therapeutic potential of riboflavin, niacin and ascorbic acid on carbohydrate metabolizing enzymes in secondary endometrial carcinoma bearing rats by Sundravel S1, Shanthi P, Sachdanandam P.(PubMed)
(8) Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. II. Synergism with combined chemotherapy action by De Loecker W1, Janssens J, Bonte J, Taper HS.(PubMed)
(9) [Ascorbic, keto and hydroxy acid metabolism in the cell nuclei of certain tumors].[Article in Russian] by Romanovich EA, Basieva FI.(PubMed)
(10) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)
(11) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)




Prostate cancer in Vitamin K's Points of View

 Kyle J. Norton(Draft Article)

Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.

Epidemiological studies focused in the synthetic version of vitamin K(Vk3) in reduced risk and treatment of prostate cancer have proven successful in certain extents. In human prostate cancer cells (DU145) implanted mice, administration of C/vitamin K(3) showed to exhibit serum alkaline DNase (DNase I) and acid DNase (DNase II) known as circulating tumour marker accompanied by a decrease in DNA expression of the tumor cells(1). Administration of vitamin C (Vit C), vitamin K3 (Vit K3), or vitamin C:vitamin K3 combinations against a prostate cancer cell line (DU145), suggest that vitamin treatment with individual vitamins affects the cytoskeleton(a series of intercellular proteins that help a cell with shape, support, and movement), the mitochondria, and other membranous components of the cell(2).
Vitamin K4 (VK4) is a synthetic version of vitamin K, inhibited proliferation in PC-3 cells with an IC50 value of about 20.94 microM, through cell cycle arrest at the S phase, disruption of the energy production in the surface of cell membrane, up regulation apoptotic and down regulation of proliferative pathways(3). Alpha-tocopheryl succinate (alpha-TOS), the redox-silent vitamin E analogue used in combination with VK3, showed to  to induce efficient cell death that resembles autoschizis(cell death), through cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation(4), In a A prostate carcinoma cell line derived from the transgenic murine prostate cancer model (TRAMP), combination of of ascorbate:menadione (VC + VK(3), induced cell death by autoschizis, included cytokeletal changes conducive to cytoplasmic blebbing, self-excisions, and progressive nuclear alteration, through axidative stress(5).the Co-administration of the vitamins enhanced the antitumour activity 5- to 20-fold, with increased cytotoxicity through redox cycling and increased oxidative stress(6). On a human prostate carcinoma cell line (DU145), the co administration also showed to enhance cytotoxicity through increased oxidative stress, subsequent membrane damage, and DNA fragmentation (7). Menaquinones (vitamin K(2) in the study of its association with overall cancer incidence and mortality, showed to is associated with a reduced risk of incident and fatal cancer(8) including prostate cancer(9).

Taking altogether, co administration of synthetic vitamin K3 and other vitamins such as vitamin C is associated to reduced risk and treatment of prostate cancer, though cell cycle arrest, up regulation of 
anti profilerative and down regulation of cancer promoter pathways or inctreased oxidative stress. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.
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References
(1) In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K(3) combination by Taper HS, Jamison JM, Gilloteaux J, Gwin CA, Gordon T, Summers JL(PubMed)
(2) Scanning electron microscopy and transmission electron microscopy aspects of synergistic antitumor activity of vitamin C - vitamin K3 combinations against human prostatic carcinoma cells by Gilloteaux J, Jamison JM, Venugopal M, Giammar D, Summers JL(PubMed)
(3) Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway by Jiang Y, Yang J, Yang C, Meng F, Zhou Y, Yu B, Khan M, Yang H(PubMed)
(4) alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate by Tomasetti M, Strafella E, Staffolani S, Santarelli L, Neuzil J, Guerrieri R(PubMed)
(5) Cell death by autoschizis in TRAMP prostate carcinoma cells as a result of treatment by ascorbate: menadione combination by Gilloteaux J, Jamison JM, Neal DR, Summers JL(PubMed)
(6) Synergistic antitumour activity of vitamins C and K3 against human prostate carcinoma cell lines by Venugopal M, Jamison JM, Gilloteaux J, Koch JA, Summers M, Hoke J, Sowick C, Summers JL.(PubMed)
(7) Flow cytometric and ultrastructural aspects of the synergistic antitumor activity of vitamin C-vitamin K3 combinations against human prostatic carcinoma cells by Jamison JM, Gilloteaux J, Venugopal M, Koch JA, Sowick C, Shah R, Summers JL(PubMed)
(8) Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) by Nimptsch K, Rohrmann S, Kaaks R, Linseisen J.(PubMed)
(9) Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) by Nimptsch K, Rohrmann S, Linseisen J.(PubMed)








Thursday, February 20, 2014

Endometrial Cancer In Foods Points of View

Kyle J. Norton(Draft Article)

The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as  BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.
Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain foods, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.
Endometrium is the inner lining of the mammalian uterus and very susceptible hormone change, particular to menstrual cycle. Endometrial cancer is a late adulthood cancer defined as a condition of which the cells of the endometrial lining of uterus have growth uncontrollable or become cancerous as a result of the alternation of cells DNA. It's the fourth most common cancer among women overall, after breast cancer, lung cancer, and bowel cancer. 

1. Cruciferous vegetables
Cruciferous vegetables are the group of  vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc. The vegetables have been suggested to reduced risk and protect against various types of cancer(5). Indole-3-carbinol (I3C), a chemical constituent found in cruciferous vegetables, in Donryu rats study showed to be effective in inhibition of spontaneous occurrence of endometrial adenocarcinoma as well as preneoplastic lesions(6). Since
 a metabolic profile of estrogens may be crucial for the endometrial carcinogenesis, Indole-3-carbinol (I3C) exerted its  anti-estrogen and induced apoptotic effects through the 2- and 4-hydroxylation pathways (catechol estrogens) and the downstream of the 16beta-hydroxylation pathway(7).

2. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. Allium vegetables have been found in many studies to have an inverse association between the frequency of use of and the risk of several common cancers(8). Purified allicin, a major ingredient of crushed garlic, showed to induced apoptosis through induction of activation of caspases-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase(9) A multi-centre case-control study of 454 endometrial cancer cases and 908 controls, allium vegetables, including garlic showed a moderate protective effect in reduced risk endometrial cancer(10). But according to the Korea Food and Drug Administration, there was no credible evidence to support a  garlic intake in reduced risk of endometrial cancer(11).

3. Tomatos
Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house. Lycopene, a major carotenoid component of tomato has been known in research community with the property to attenuate the risk of endometrial cancer., through cellular effects, either by chemical oxidation or by enzymatic cleavage inside the cells(12). In endometrial (ECC-1) cancer cell,composition of lycopene and atRA inhibited Insulin-like growth factors (IGFs) -I-stimulated cell cycle progression through G1 to S phase and decreased (retinoblastoma protein (pRb)) tumor suppressor protein dysfunction(13) or cell cycle progression(14). In the comparison of the effects of  lycopene and alpha- and beta-carotene in endometrial cancer, lycopene is more potent in inhibited basal endometrial cancer cell proliferation, and suppressed insulin-like growth factor-I-
stimulated growth(15).

4. Organic soybean
Soybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profit and a healthy foods.
Phytochemicals such as daidzein, genistein, or glycitein found in soy and other legumes have been speculated to reduce the risk of endometrial cancer and specially in lean women(16).. According to the University of Hawaii Cancer Center, greater consumption of isoflavone-containing foods is associated with a reduced risk of endometrial cancer in nonhysterectomized postmenopausal women(17). In Estrogen-induced proliferation of endometrial epithelial cells, genistein found in legime and organic soy inhibited the proliferative effects of estrogen on endometrial adenocarcinoma cells presumably through activation of stromal cell ERβ(18). But In a total of 666 visits among 224 participants study conducted by University of Southern California, showed that there was no evidences to support of the effects of ISP supplementation onendometrial thickness or on the odds of endometrial hyperplasia and cancer in postmenopausal women(19).

5. Whole grain
It is suggested that whole grain reduced risk of endometrial cancer through its interaction of  sex hormone metabolism and body fat in a study of Cancer and Health cohort of 29,875 women aged 50-64 years at enrollment in 1993-1997(20).  Lignan, a chemical constituents found abundantly in whole-grain cereals, beans, berries, nuts, in animals has shown clear anticarcinogenic effects(21). A study of 23,014 Iowa women, aged 55-69 years in 1986 conducted by the University of Minnesota, indicated that an inverse association between whole grain intake and endometrial cancer and may protect against endometrial cancer among never-users of hormone replacement therapy(22). Also in a review of the literature, the University of Minnesota showed there is a striking consistency in reduced risk edometrial cancers associated with intake of whole grain(23).

6. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. The University of Bristol study showed that there is some positive evidence for risk reduction of  endometrial cancers with green tea consumption(24). (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, inhibited endometrial cancer cell line through inhibiting ERK activation and inducing apoptosis via ROS generation and p38 activation(25). The a population-based case-control study in urban Shanghai indicated that the reduction of risk of endometrial cancer may be  only limit to premenopausal women(26)). Some studies suggested that  tea consumption may reduce the risk of endometrial cancer but further prospective studies are needed(27).

7. Coffee
Coffee made from the roasted seeds of the genus Coffee, belonging to the family Rubiaceae native to southern Arabia. Strong evidence suggested that  drinking coffee reduced risk of endometrial cancer. The study of showed a correlation of caffeinated coffee intake associated with lower endometrial cancer risk among obese postmenopausal women(27) but the association with decaffeinated coffee remains unclear. In a prospective cohort study, conducted by the Harvard School of Public Health, Boston, indicated that Drinking of coffee, may reduce endometrial cancer risk, but addition of substantial sugar and cream to coffee could offset any potential benefits(28). The The National Institute of Environmental Medicine study also showed a positive effect of coffee in reduced risk of endometrial cancer, especially among women with excessive body weight(29).

8.  Fatty fish
Fatty fish containing a large amounts of omega-3 fatty acids may be associated to reduced risk of endometrial cancer, but not other types of fish, according to the nationwide case-control study in Sweden(30).The Ohio State University College of Medicine and the Fred Hutchinson Cancer Research Center study showed that long-chain ω-3 (n-3) polyunsaturated fatty acids (PUFAs), derived from marine sources, consisted a anti-inflammatory effect thus reducing risk of endometrial cancer, restricted to overweight and obese women(31). In the investigation of Tohoku University Graduate School of Medicine, the study indicated that  higher intake of vegetables, peanuts, fish, and boiled egg was associated with a reduced risk for EEA(32). Unfortunately, some researchers suggested that there is evidence to support an association between meat or fish intakes or meat mutagens and endometrial cancer(33).

9. Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
According to the study by the University of Athens Medical School, increased intake of monounsaturated fat, mostly olive oil, was associated with endometrial cancer risk reduction and increase olive oil intake by 1 standard deviation, risk of endometrial cancer reduced by 26% (34). In a 84 women study with intact uterus admitted to the same teaching hospital in Athens, showed that risk of endometrial cancer is reduced with intake Retinol, nicotinic acid, vitamin B- 6, and riboflavin, but olive oil was highly suggestive(35). Other researchers suggested since the incidence of cancer overall in Mediterranean countries is lower than in Scandinavian countries, the United Kingdom, and the United States, it may be result of healthy traditional Mediterranean diet(36).

Taking altogether, without going into reviews, intake of above list foods are associated to reduced risk and treatment of endometrial cancer. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.
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References
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)
(5) Cruciferous vegetables and cancer risk in a network of case-control studies by Bosetti C, Filomeno M, Riso P, Polesel J, Levi F, Talamini R, Montella M, Negri E, Franceschi S, La Vecchia C.(PubMed)
(6) Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol by Kojima T, Tanaka T, Mori H(PubMed)
(7) Effects of estrogens and metabolites on endometrial carcinogenesis in young adult mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine by Takahashi M, Shimomoto T, Miyajima K, Yoshida M, Katashima S, Uematsu F, Maekawa A, Nakae D.(PubMed)
(8) Onion and garlic use and human cancer by Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, Talamini R, Giacosa A, La Vecchia C.(PubMed)
(9) Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells by Oommen S, Anto RJ, Srinivas G, Karunagaran D.(PubMed)
(10) Allium vegetables intake and endometrial cancer risk by Galeone C, Pelucchi C, Dal Maso L, Negri E, Montella M, Zucchetto A, Talamini R, La Vecchia C.(PubMed)
(11) Garlic intake and cancer risk: an analysis using the Food and Drug Administration's evidence-based review system for the scientific evaluation of health claims by Kim JY, Kwon O(PubMed)
(12) The role of lycopene and its derivatives in the regulation of transcription systems: implications for cancer prevention by Sharoni Y, Linnewiel-Hermoni K, Zango G, Khanin M, Salman H, Veprik A, Danilenko M, Levy J.(PubMed)
(13) Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1 by Nahum A, Zeller L, Danilenko M, Prall OW, Watts CK, Sutherland RL, Levy J, Sharoni Y.(PubMed)
(14) Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-cdk2 complexes by Nahum A, Hirsch K, Danilenko M, Watts CK, Prall OW, Levy J, Sharoni Y.(PubMed)
(15) Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene by Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M, Sharoni Y.(PubMed)
(16) Phytoestrogen consumption and endometrial cancer risk: a population-based case-control study in New Jersey by Bandera EV1, Williams MG, Sima C, Bayuga S, Pulick K, Wilcox H, Soslow R, Zauber AG, Olson SH(PubMed)
(17) Legume, soy, tofu, and isoflavone intake and endometrial cancer risk in postmenopausal women in the multiethnic cohort study by Ollberding NJ1, Lim U, Wilkens LR, Setiawan VW, Shvetsov YB, Henderson BE, Kolonel LN, Goodman MT(PubMed)
(18) Genistein effects on stromal cells determines epithelial proliferation in endometrial co-cultures by Sampey BP1, Lewis TD, Barbier CS, Makowski L, Kaufman DG(PubMed)
(19) Effect of isoflavone soy protein supplementation on endometrial thickness, hyperplasia, and endometrial cancer risk in postmenopausal women: a randomized controlled trial by Quaas AM1, Kono N, Mack WJ, Hodis HN, Felix JC, Paulson RJ, Shoupe D.(PubMed)
(20) Whole grain, dietary fiber, and incidence of endometrial cancer in a Danish cohort study by Aarestrup J1, Kyrø C, Christensen J, Kristensen M, Würtz AM, Johnsen NF, Overvad K, Tjønneland A, Olsen A(PubMed)
(21) Lignans and human health by Adlercreutz H.(PubMed)
(22) Whole grain intake and incident endometrial cancer: the Iowa Women's Health Study by Kasum CM1, Nicodemus K, Harnack LJ, Jacobs DR Jr, Folsom AR; Iowa Women's Health Study(PubMed)
(23) Whole grain intake and cancer: a review of the literature by Jacobs DR Jr1, Slavin J, Marquart L(PubMed)
(24) Green tea and green tea catechin extracts: an overview of the clinical evidence by Johnson R1, Bryant S, Huntley AL(PubMed)
(25) (-)-Epigallocatechin-3-gallate induces apoptosis in human endometrial adenocarcinoma cells via ROS generation and p38 MAP kinase activation by Manohar M1, Fatima I, Saxena R, Chandra V, Sankhwar PL, Dwivedi A(PubMed)
(26) [Green tea consumption and the risk of endometrial cancer: a population-based case-control study in urban Shanghai].[Article in Chinese] by Gao J1, Xiang YB, Xu WH, Shao CX, Ruan ZX, Cheng JR, Shu XO, Gao YT(PubMed)
(26) Tea consumption and risk of endometrial cancer: a metaanalysis by Tang NP1, Li H, Qiu YL, Zhou GM, Ma J(PubMed)
(27) Caffeinated coffee, decaffeinated coffee and endometrial cancer risk: a prospective cohort study among US postmenopausal women by Giri A1, Sturgeon SR, Luisi N, Bertone-Johnson E, Balasubramanian R, Reeves KW(PubMed)
(28) A prospective cohort study of coffee consumption and risk of endometrial cancer over a 26-year follow-up by Je Y1, Hankinson SE, Tworoger SS, De Vivo I, Giovannucci E(PubMed)
(29) Coffee drinking and risk of endometrial cancer--a population-based cohort study by Friberg E1, Orsini N, Mantzoros CS, Wolk A(PubMed)
(30) Fatty fish consumption lowers the risk of endometrial cancer: a nationwide case-control study in Sweden by Terry P1, Wolk A, Vainio H, Weiderpass E(PubMed)
(31) Associations of long-chain ω-3 fatty acids and fish intake with endometrial cancer risk in the VITamins And Lifestyle cohort by Brasky TM1, Neuhouser ML, Cohn DE, White E(PubMed)
(32) Food intake and the risk of endometrial endometrioid adenocarcinoma in Japanese women by Takayama S1, Monma Y, Tsubota-Utsugi M, Nagase S, Tsubono Y, Numata T, Toyoshima M, Utsunomiya H, Sugawara J, Yaegashi N(PubMed)
(33) A prospective investigation of fish, meat and cooking-related carcinogens with endometrial cancer incidence by Arem H1, Gunter MJ, Cross AJ, Hollenbeck AR, Sinha R(PubMed)
(34) Dietary factors and the risk of endometrial cancer: a case--control study in Greece by Tzonou A1, Lipworth L, Kalandidi A, Trichopoulou A, Gamatsi I, Hsieh CC, Notara V, Trichopoulos D(PubMed)
(35) Diet in relation to endometrial cancer risk: a case-control study in Greece by Petridou E1, Kedikoglou S, Koukoulomatis P, Dessypris N, Trichopoulos D(PubMed)
(36) Cancer and Mediterranean dietary traditions by Trichopoulou A1, Lagiou P, Kuper H, Trichopoulos D.(PubMed)







Prostate cancer in Vitamin B6's Points of View

 Kyle J.Norton(Draft Article)

Vitamin B6, also known as pyridoxine, is a water soluble vitamin found abundantly in green peas, yams, broccoli, asparagus and turnip greens,Peanuts, sunflower seeds, cashews and hazelnuts, meat, fish etc., with functions of amino acid, carbohydrate  metabolism, brain health, and liver detoxification, etc.

Prostate cancer, a second leading cause of cancer death in men is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body.
.
Epidemiological studies, focusing pyridoxine in reduced risk and treatment of prostate cancer have been inconclusive. Study of the  link between intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans, showed no evidence for associations between B vitamins (folate, B12, and B6) and PC risk(1) and In the one-carbon metabolism and prostate cancer risk, researcher found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer(2).  Dietary methyl groups(methionine, one-carbon units and choline (or the choline metabolite betaine) showed a a protective effect on the development of higher grades of prostate cancer in the "Hi-myc" mouse model of prostate cancer(3). Other suggestion indicated that high vitamin B-6 intake may improve prostate cancer survival among men with a diagnosis of localized-stage disease(4). A case-control study of diet and prostate cancer, included 328 men diagnosed with prostate cancer before the age of 75 years and 328 age-matched population controls, vitamin B6 was associated to reduced risk of prostate cancer(5)

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References
(1) Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans by Vidal AC, Grant DJ, Williams CD, Masko E, Allott EH, Shuler K, McPhail M, Gaines A, Calloway E, Gerber L, Chi JT, Freedland SJ, Hoyo C.(PubMed)
(2) Dietary factors of one-carbon metabolism and prostate cancer risk by Weinstein SJ, Stolzenberg-Solomon R, Pietinen P, Taylor PR, Virtamo J, Albanes D.(PubMed)
(3) Progression of prostate carcinogenesis and dietary methyl donors: temporal dependence by Shabbeer S, Williams SA, Simons BW, Herman JG, Carducci MA.(PubMed)
(4) One-carbon metabolism-related nutrients and prostate cancer survival by Kasperzyk JL, Fall K, Mucci LA, Håkansson N, Wolk A, Johansson JE, Andersson SO, Andrén O.(PubMed)
(50) A case-control study of diet and prostate cancer by Key TJ, Silcocks PB, Davey GK, Appleby PN, Bishop DT(PubMed)

Wednesday, February 19, 2014

Prostate cancer in Vitamin B2's Points of View


Kyle J.Norton(Draft Article)

Vitamin B2 also known as Riboflavin, is a water-soluble, yellow-orange organic compound found abundantly in milk, meat, eggs, nuts, enriched flour, green vegetables, etc. The vitamin is essential for normal cellular growth and function and best known for converting energy from protein, fat, and carbohydrates during metabolism and its antioxidant effects in oxidation-reduction reactions.

Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.
Over expression of riboflavin carrier protein (RCP) in prostate cancer patient may ve used as a marker in -targeted diagnosis and for the assessment of vascular metabolism in tumors(6). In localized both androgen-dependent and independent prostate cancer cell lines, Antibodies to chicken RCP inhibited incorporation of tritiated thymidine into DNA and prevented riboflavin uptake in PC3 prostate cancer cells(7). Other suggestion of elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer(8).

Epidmeiological studies, linking vitamin B2 in reduced risk of prostate cancer have produced inconsistent results. In prostae cancer cell line cancer (LnCap), vitamin B2 intakes were not associated with prostate cancer survival(1) and dietary supplements, including vitamn B2 effective treatments for PC patients is not supported by sound clinical evidence(2).  Luckily, in the study of Cancer Research and Product Development Laboratory, Immunal Ltd, active mixture AM: L-arginine, L-histidine, L-methionine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ascorbate, D-biotin, pyridoxine, riboflavin, adenine, L(-)malate), induced apoptosis through the mitochondrial pathway and G1 arrest in PC-3 cells and in PC-3 xenografts(3). Also in the interaction of interaction between β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) and riboflavin (RF) indicated that both RF-βCD and RF-HPβCD complexes were cytotoxic to PC3 prostate cancer cells(4). Other suggestion showed a weak associations between prostate cancer incidence and dietary intake of riboflavin and between riboflavin intake and prostate cancer mortality(5). But in the study of the role of diet in prostate cancer, researchers suggested that intake of  linoleic acid and riboflavin (in subjects 50 years and over) could be protective when compared with control subjects(10)and the study of the effects of irradiated riboflavin on androgen-independent human, by Universidade Estadual de Campinas, showed  that riboflavin photoproducts are cytotoxic to these cells in a FasL-Fas-dependent manner, through inhibited matrix-degrading proteases(invloved both the process of ECM remodeling and angiogenesis, and in a potential causal relationship between these processe) caused downregulation of VEGF(vascular endothelial growth factor ) and upregulation of TIMP1(inhibitor of metalloproteinases)(9).

Taking altogether, riboflavin carrier protein (RCP) may be used as a marker in targeted diagnosis of prostate cancer and  Vitamin B2 may be  considered as a vital component of any treatment plan instead of sole means of cancer prevention and treatment in Prostate cancer patients. Over doses for a prolong period may cause symptoms of skin rashes, hypersensitivity, high blood pressure etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.
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References
(1) One-carbon metabolism-related nutrients and prostate cancer survival by Kasperzyk JL, Fall K, Mucci LA, Håkansson N, Wolk A, Johansson JE, Andersson SO, Andrén O(PubMed)
(2) Dietary supplements and prostate cancer: a systematic review of double-blind, placebo-controlled randomised clinical trials by Posadzki P, Lee MS, Onakpoya I, Lee HW, Ko BS, Ernst E.(PubMed)
(3) A mixture of amino acids and other small molecules present in the serum suppresses the growth of murine and human tumors in vivo by Kulcsár G, Gaál D, Kulcsár PI, Schulcz Á, Czömpöly T(PubMed)
(4) Non-inclusion complexes between riboflavin and cyclodextrins by de Jesus MB, Fraceto LF, Martini MF, Pickholz M, Ferreira CV, de Paula E(PubMed)
(5) Dietary intake of B vitamins and methionine and prostate cancer incidence and mortality by Bassett JK, Severi G, Hodge AM, Baglietto L, Hopper JL, English DR, Giles GG.(PubMed)
(6) Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors by Jayapaul J, Arns S, Lederle W, Lammers T, Comba P, Gätjens J, Kiessling F(PubMed)
(7) Biochemical characterization of riboflavin carrier protein (RCP) in prostate cancer by Johnson T, Ouhtit A, Gaur R, Fernando A, Schwarzenberger P, Su J, Ismail MF, El-Sayyad HI, Karande A, Elmageed ZA, Rao P, Raj M(PubMed)
(8) One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites by Johansson M, Van Guelpen B, Vollset SE, Hultdin J, Bergh A, Key T, Midttun O, Hallmans G, Ueland PM, Stattin P(PubMed)
(9) A possible anti-proliferative and anti-metastatic effect of irradiated riboflavin in solid tumours by de Souza Queiroz KC, Zambuzzi WF, Santos de Souza AC, da Silva RA, Machado D, Justo GZ, Carvalho HF, Peppelenbosch MP, Ferreira C(PubMed)
(10) The role of diet in prostate cancer by Kaul L, Heshmat MY, Kovi J, Jackson MA, Jackson AG, Jones GW, Edson M, Enterline JP, Worrell RG, Perry SL(PubMed)

Tuesday, February 18, 2014

Prostate cancer in Vitamin D's Points of View

Kyle J. Norton(Draft Article)

Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.
The widespread of prostate cancer, once considered as a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to spread to younger age population. Suggestions emerged of over consuming bad fats in any time in history accompanied with unhealthy diet and life style may be the possible causes of the disease, linking to the economic prosperity over 2 decades. Herbal medicine for diseases' management have been prescribed in folk medicine over thousands of year as one of best medicine of nature in preventing and treating diseases, including prostate cancer.

Genetic mutation
Genetic mutation of Vitamin D-deactivating enzyme CYP24A1may be associated to increased risk of prostate cancer. In a Korean cohort suggested that five CYP24A1 sequence variants (rs2248461,  rs2248359, rs602299, rs2585428, rs4809959 had a significant association with prostate cancer risk(1);
vitamin D receptor (VDR) gene (two VDR sequence variants (rs2408876 and rs2239182), may play an important role in the onset and progression of prostate cancer(2). Others study of vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer showed an conflict result of that genotypes of CYP27B1 and CYP24A1 were not associated with prostate cancer risk, but polymorphisms in the VDR gene may be(3)(4)(5). In common genetic variation of the calcium-sensing receptor(CaSR), the Harvard School of Public Health showed that CaSR may be involved in PCa progression(5a)

Vitamin D plasma
Suggestions of plasma used in measurement of risk of prostate have been controversial with many inconsistent results, epidemiological. The population-based cohort study of 1476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D], showed no evidence of serum vitamin D levels measured after diagnosis associated to prostate cancer prognosis(6) and  according to the Oregon Health & Science University prospective cohort of older men also found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer.(6a). But according to the Harvard Medical School, suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)2D may play an important role in preventing prostate cancer progression(7) and  higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis(8).
In the variation of  above, some researchers suggested that  plasma 25(OH)D levels associated to common variation among several vitamin D-related genes((CYP27A1, CYP2R1, CYP27B1, GC, CYP24A1, RXRA, and VDR) and calcium-sensing receptor (CaSR)were associated with lethal prostate cancer risk(9)(10)(11). A report of survival in veterans with prostate cancer indicated a veterans who are initially vitamin D deficient and both initial and follow-up vitamin D deficiency are associated with decreased likelihood of survival after prostate cancer diagnosis(12). Other suggestions, linking vitamin D in reduced risk of prostate cancer and  prostate cancer-related health disparities in African-American men were greatly involved at least in part the result of widespread hypovitaminosis D within the African-American population.(15).


The efficacy
Vitamin D most active form, 1,25D(3) in an experiment of a stable prostate cancer cell line PC3 with CYP24A1 promoter inhibited gene expression of CYP24A1 through enhancement and regulation of  a protein kinase CK2 selective inhibitor(13); exhibited tumor suppressive miRNAs in patient prostate tissue, thus decreased proliferation in primary cells and cancer cells and suppressed migration and clonal growth of prostate cancer cell in a miRNA-dependent manner(14). A report from the Medical University of South Carolina, showed that vitamin D(3) supplementation at 4000 IU/d for 1 year, in patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation(16) and eliminated any significant differences in circulating concentrations of 25(OH)D between African American and white men(17). Unfortunately, the University of Oslo study within Norwegian health studies indicated a increased risk of prostate cancer related to a high 25(OH)D concentration only during the summer and autumn due to vitamin D itself or to other factors associated with sun exposure(18). The discrepancy between the results of studies of solar exposure and studies of serum 25-OHD may be related to methodological differences and to uncertainties regarding the critical period for vitamin D exposure(19). The same author also suggested that low levels of UV radiation/vitamin D are indeed associated with an increased risk of prostate cancer in individual men(20).

Taking altogether, without going into reviews, although it is controversial, vitamin D may be effectively and selectively in reduced risk and treatment for prostate cancer in hypovitamin D deficient men and without exposure to UV sunlight and the disagreement of amount of vitamin D intake and plasma level in reduced risk and treatment of prostate cancer may still need further studies. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.
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References
(1) Genetic variants in the CYP24A1 gene are associated with prostate cancer risk and aggressiveness in a Korean study population. by Oh JJ1, Byun SS2, Lee SE2, Hong SK2, Jeong CW2, Choi WS3, Kim D4, Kim HJ5, Myung SC6(PubMed)
(2) Genetic variations in VDR associated with prostate cancer risk and progression in a Korean population by Oh JJ, Byun SS, Lee SE, Hong SK, Jeong CW, Kim D, Kim HJ, Myung SC(PubMed)
(3) Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer by Holick CN, Stanford JL, Kwon EM, Ostrander EA, Nejentsev S, Peters U.(PubMed)
(3) Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review by Chen L, Davey Smith G, Evans DM, Cox A, Lawlor DA, Donovan J, Yuan W, Day IN, Martin RM, Lane A, Rodriguez S, Davis M, Zuccolo L, Collin SM, Hamdy F, Neal D, Lewis SJ(PubMed)
(5) Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk by Raimondi S, Johansson H, Maisonneuve P, Gandini S(PubMed)
(5a) Common genetic variation of the calcium-sensing receptor and lethal prostate cancer risk by Shui IM, Mucci LA, Wilson KM, Kraft P, Penney KL, Stampfer MJ, Giovannucci E(PubMed)

(6) Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis by Holt SK, Kolb S, Fu R, Horst R, Feng Z, Stanford JL.(PubMed)
(7) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer by Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D, Giovannucci EL, Ma J(PubMed)
(8) Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer by Fang F, Kasperzyk JL, Shui I, Hendrickson W, Hollis BW, Fall K, Ma J, Gaziano JM, Stampfer MJ, Mucci LA, Giovannucci E(PubMed)
(9) Vitamin D-related genetic variation, plasma vitamin D, and risk of lethal prostate cancer: a prospective nested case-control study by Shui IM, Mucci LA, Kraft P, Tamimi RM, Lindstrom S, Penney KL, Nimptsch K, Hollis BW, Dupre N, Platz EA, Stampfer MJ, Giovannucci E(PubMed)
(10) Common genetic variation of the calcium-sensing receptor and lethal prostate cancer risk by Shui IM, Mucci LA, Wilson KM, Kraft P, Penney KL, Stampfer MJ, Giovannucci E(PubMed)
(11) Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk by Ahn J, Albanes D, Berndt SI, Peters U, Chatterjee N, Freedman ND, Abnet CC, Huang WY, Kibel AS, Crawford ED, Weinstein SJ, Chanock SJ, Schatzkin A, Hayes RB; Prostate, Lung, Colorectal and Ovarian Trial Project Team(PubMed)
(12)Vitamin d and prostate cancer survival in veterans by Der T1, Bailey BA2, Youssef D1, Manning T3, Grant WB4, Peiris AN(PubMed)
(13) Inhibition of protein kinase CK2 reduces Cyp24a1 expression and enhances 1,25-dihydroxyvitamin D(3) antitumor activity in human prostate cancer cells by Luo W, Yu WD, Ma Y, Chernov M, Trump DL, Johnson CS.(PubMed)
(14) Tumor suppressor microRNAs, miR-100 and -125b, are regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in patient tissue by Giangreco AA, Vaishnav A, Wagner D, Finelli A, Fleshner N, Van der Kwast T, Vieth R, Nonn L.(PubMed)
(15) Vitamin D3 supplementation, low-risk prostate cancer, and health disparities by Hollis BW, Marshall DT, Savage SJ, Garrett-Mayer E, Kindy MS, Gattoni-Celli S(PubMed)
(16) Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance by Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, Ambrose LH, Kindy MS, Gattoni-Celli S.(PubMed)
(17) Vitamin D3 supplementation (4000 IU/d for 1 y) eliminates differences in circulating 25-hydroxyvitamin D between African American and white men by Garrett-Mayer E, Wagner CL, Hollis BW, Kindy MS, Gattoni-Celli S.(PubMed)
(18) Vitamin D, season, and risk of prostate cancer: a nested case-control study within Norwegian health studies by Meyer HE, Robsahm TE, Bjørge T, Brustad M, Blomhoff R.(PubMed)
(19) Vitamin D, sunlight, and the epidemiology of prostate cancer by Schwartz GG.(PubMed)
(20) Vitamin D and the epidemiology of prostate cancer by Schwartz GG.(PubMed)