Ovarian Cancer in B12 Points of View

  Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States were diagnosed with ovarian cancer and 13,850 deaths.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some vitamins have showed to inhibit the progression of cancer with little or no side effects.

Vitamin B12, also known as cobalamin, a water-soluble vitamin, found abundantly in a variety of foods, such as fish, shellfish, meat, eggs, dairy products, etc. plays an important role in regulating the functions of nervous system and formation of blood.

Epidemiological studies, linking vitamin B12 in reduced risk of ovarian cancer have drawn into inconclusive results. Suggestion of Folate, methionine, vitamin B(6) and vitamin B(12) may influence carcinogenesis due to their roles in the one-carbon metabolism pathway. In a study among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008, have indicated that One-carbon metabolism(metabolic network of interdependent biosynthetic pathways) related nutrients,  may lower ovarian cancer risk(1). Nitrosylcobalamin (NO-Cbl), a chemotherapeutic pro-drug derived from vitamin B12 has been found effectively in antiproliferative activity against several human cancer cell lines, including ovarian carcinoma (NIH-OVCAR-3) cells, through induction of apoptosis via a death receptor/caspase-8 pathway(2). In patients with epithelial ovarian cancer under treatment of Paclitaxel (T) and Carboplatin (J) combination chemotherapy, vitamin B12 was effective in relieving symptoms of arthralgia and muscular pain(3).

Taking altogether, vitamin B12 may be effective in reduced riak and treatment of ovarian cancer, but large sample and multu centers studies to validate its effects are necessary. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying. Over doses of the vitamin may induce symptoms of toxicity, including headache, giddiness and abnormal heart functioning, etc., please make sure to follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR¹, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)
(2) Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L/TRAIL receptor DR4 by Tang Z¹, Bauer JA, Morrison B, Lindner DJ.(PubMed)
(3) [The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in paclitaxel combination chemotherapy for epithelial ovarian carcinoma].

[Article in Japanese by Fujii K¹, Okamoto S, Saitoh K, Sasaki N, Takano M, Tanaka S, Kudoh K, Kita T, Tode T, Kikuchi Y.(PubMed)

Ovarian Cancer in Folate Points of View

 Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States were diagnosed with ovarian cancer and 13,850 deaths.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.
Folate, also known as folic acid, vitamin B9, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention.

Epidemiological studies, focusing folate in reduced risk of ovarian cancer have been inconclusive.
Folate, a member of B vitamin plays an important role in DNA synthesis and methylation, may process an anti proliferative effect in ovarain cancer cell lines. The Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires, showed a little evidence to support the effect of folate in reduced risk of ovarian cancer(1) and  ovarian cancer survival(2). Other researchers suggested that no specific dietary factors are consistently associated with ovarian cancer risk, including folate(3), neither folate intake, MTHFR C677T polymorphism(4) nor one-carbon metabolism(5)
A prospective case-control study of the effect of Folic acid and methylenetetrahydrofolate reductase (MTHFR) against ovarian cancers in 215 ovarian cancer patients and 218 controls (all Chinese) between Jan. 2004 and Jan. 2007, indicated a result of a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake(6). Intravenous administration of composition of  FA-NP showed more potent in anti proliferation than NP against both SKOV3 cells and SKOV3/TAX cells, but at the same dose failed to induce apoptosis and inhibit tumor nodule number. Of these results, researchers suggested that the combined use of both FN-NP locally and targetly might prolong the survival time in patients with drug-resistant ovarian cancer(6). The Brigham and Women's Hospital study also supported the evidence of one-carbon metabolism related nutrients, especially vitamin B(7) and methionine inlowering ovarian cancer risk, with a 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008(8).

Taking all together, there are either enough evidences supported or unsupported  the effectiveness of folate in reduced risk of ovarian cancer. Further studies with large sample size and mutli centers studies are necessary to clarify the effect of folate in ovarian cancer risk. At the mean time as always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
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References
(1) Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer by Webb PM¹, Ibiebele TI, Hughes MC, Beesley J, van der Pols JC, Chen X, Nagle CM, Bain CJ, Chenevix-Trench G; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group.(PubMed)
(2) Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival by Dixon SC¹, Ibiebele TI², Protani MM¹, Beesley J², Defazio A³, Crandon AJ⁴, Gard GB⁵, Rome RM⁶, Webb PM¹, Nagle CM⁷; on behalf of the Australian Ovarian Cancer Study Group.(PubMed)
(3) Dietary intake and ovarian cancer risk: a systematic review, by Crane TE¹, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)
(4) Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis by Li C¹, Chen P, Hu P, Li M, Li X, Guo H, Li J, Chu R, Zhang W, Wang H.(PubMed)
(5) Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor alpha expression in ovarian tumors by Kotsopoulos J¹, Hecht JL, Marotti JD, Kelemen LE, Tworoger SS(PubMed)
(6) Folate intake and methylenetetrahydrofolate reductase gene polymorphisms as predictive and prognostic biomarkers for ovarian cancer risk by Zhang L¹, Liu W, Hao Q, Bao L, Wang K.(PubMed)
(7) Folic acid-coupled nano-paclitaxel liposome reverses drug resistance in SKOV3/TAX ovarian cancer cells by Tong L¹, Chen W, Wu J, Li H.(PubMed)
(8) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR¹, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)

Ovarian Cancer in Vitamin B6 Points of View

 Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries. It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.

Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some vitamins have showed to inhibit the progression of cancer with little or no side effects.
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.

Epidemiological studies, linking vitamin B6 in reduced risk of ovarian cancer have been inconsistent. 
The study of the Brigham and Women's Hospital, Boston, indicated that intake of one-carbon metabolism related nutrients, especially vitamin B(6) and methionine, may lower ovarian cancer risk (1). In 80,254 Nurses' Health Study participants, during 22 years of follow-up (1980-2002), researchers found little evidence to support dietary folate, methionine, and vitamin B(6) in related ovarian cancer risk(2), But
in the study to compare the effectiveness of acupuncture plus vitamin B6 PC6 points injection of 142 patients, between March 1, 2006, and June 30, 2008 indicated that acupuncture plus vitamin B6 PC6 points injection relieved nausea and vomiting in patients with ovarian cancer, undergoing a highly emetogenic chemotherapy regimen(3). In a  total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) conducted by the Albert Einstein Cancer Center, showed that although  administration of pyridoxine significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with  cisplatin (DDP) and hexamethylmelamine (HMM) regimens(4). In the assessed dietary intakes and factors associated with diet in women with family history of breast and/or ovarian cancer (FHBOC) study, suggest that women with FHBOC should be encouraged to meet dietary guidelines for cancer prevention, including intake of vitamin B6(5).

Taking altogether, vitamin B6 may be associated to reduced risk and treatment of ovarian cancer when it is used in conjunction with acupuncture, but further study with large sample and multi center studies are necessary to improve the validation. Over doses may induced the symptoms of difficulty coordinating movement, numbness, sensory changes, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

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References
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M¹, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A¹, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E¹, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1)Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR¹, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)
(2) Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer by Tworoger SS¹, Hecht JL, Giovannucci E, Hankinson SE.(PubMed)

(3) Vitamin B6 points PC6 injection during acupuncture can relieve nausea and vomiting in patients with ovarian cancer by You Q¹, Yu H, Wu D, Zhang Y, Zheng J, Peng C.(PubMed)
(4) Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group by Wiernik PH¹, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J.(PubMed)
(5) Diet and predictors of dietary intakes in women with family history of breast and/or ovarian cancer by McEligot AJ¹, Mouttapa M, Ziogas A, Anton-Culver H.(PubMed)

Ovarian Cancer in Vitamin K Points of View

 Kyle J. Norton
Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
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.

Researchers at the Showa University indicated that vitamin K may process the anti wide array of human cancer cell lines properties through differentiation and apoptosis(1). DR. Shibayama-Imazu, the leader of the research team said that these inductions may be through interruption of the morphological changes and DNA fragmentation via the loss of mitochondrial membrane potential (DeltaPsim caused by superoxide(1).  Vitamin K2 also induced apoptosis of human ovary cancer cells (TYK-nu cells), through the process of production of superoxide, induced oxidative stress in mitochondria might damage mitochondrial membranes(2). In PA-1 ovarian cancer cells, vitamin exhibited apoptosis through increased in the synthesis of TR3 and the accumulation of TR3 in mitochondria and in nuclei via a JNK signaling pathway(3). Against human ovarian carcinoma cell line (MDAH 2774), the composition of VC (ascorbic acid) and VK3 (menadione), inhibited cell proliferation through DNA degradation(4) and exposure to the composition also expressed the anti proliferation of cell death through autoschizis (43%), apoptosis (3%), and oncosis (1.9%)(5). In the comparison of the effect of vitamin K(2) (menaquinone 4) and  geranylgeraniol (GGO)inhuman cancer cell line, showed that GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation and induced apoptosis in both ovarian cell lines(6). Study of the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma, indicated a positive effects of the composition in induced cell death  (displayed characteristics of both apoptosis and necrosis), through cycle arrest and degradation of chromosomal DNA(7).

Taking all together, vitamin VK2 and VK3 are found effectively in reduced risk and treatment of ovarian cancer through activation of cell death mechanism, via activation of RSO, cell cycle arrest,  and inhibition of cell proliferation via degradation of DNA. Large sample and multi centers studies to validate this effectiveness are necessary. 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


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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References
(1) Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential. by Shibayama-Imazu T¹, Aiuchi T, Nakaya K. (PubMed)
(2) Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells by Shibayama-Imazu T¹, Sonoda I, Sakairi S, Aiuchi T, Ann WW, Nakajo S, Itabe H, Nakaya K.(PubMed)
(3) Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei by Sibayama-Imazu T¹, Fujisawa Y, Masuda Y, Aiuchi T, Nakajo S, Itabe H, Nakaya K.(PubMed)
(4) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J¹, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)
(5) Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment by Gilloteaux J¹, Jamison JM, Arnold D, Taper HS, Von Gruenigen VE, Summers JL.(PubMed)
(6) Vitamin K(2) selectively induced apoptosis in ovarian TYK-nu and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol by Shibayama-Imazu T¹, Sakairi S, Watanabe A, Aiuchi T, Nakajo S, Nakaya K.(PubMed)
(7) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE¹, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)

Ovarian Cancer in Vitamin E Points of View

By Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovarian cells,  It is one of most common cancer in US. According to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States were diagnosed with ovarian cancer and 13,850 deaths.

Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.

 Vitamin E,  a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(2), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc.

Epidemiological studies, linking serum of vitamin E in the risk of ovarian cancer have produced inconsistent results.  Serum levels of vitamin are not associated to ovarian cancer risk, according to Tampere University Central Hospital and (1) but the study by Johns Hopkins University School of Hygiene and Public Health, indicated that the higher serum alpha-tocopherol levels are associated with an increased risk of ovarian cancer but diminished after adjustment for cholesterol(2). Other study suggested that lower alpha-tocopherol concentrations may be associated with the toxicity of  chemotherapy(3).

Alpha-TEA , a novel vitamin E analogue found to induce apoptosis a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture and inhibit tumor burden and metastasis in a syngeneic mouse mammary tumor model,(4). Other study suggested that vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, excluding normal human mammary epithelial cells(5). In SK-OV-3 human ovarian adenocarcinoma along with its multi-drug resistant version SK-OV-3-paclitaxel-resistant (TR) cells, combination treatment of vitamin E co-loaded with curcumin and paclitaxel(a mitotic inhibitor) exhibited  a three-fold tumor inhibition with each of these cell lines(6). According to the University of Strathclyde, intravenous administration tocotrienol-rich fraction (TRF), showed to exhibit tumor regression and improved animal survival in a murine xenograft model(7). In MDAH2774 human ovarian cancer cells combined treatment of Adenovirus-mediated mda-7 (Ad-mda7) plus VES inhibited tumor progression through activation of two apoptotic extrinsic and intrinsic pathways (specifically Fas expression and cleavage of Bid and caspase-8 and disruption of mitochondrial in activation of downstream capase-9 and caspase-3 via cytochrome C releasE) but not the normal fibroblasts(8). and treatment with Ad-mda7-mediated alone induced apoptosis of  human ovarian cancer cells via activation of the Fas-FasL signaling pathway(9).

Taking altogether,  vitamin E succinate and analogue may be effective in reduced risk and treatment of ovarian cancer. Large sample size and multi center studies to validate the claims are necessary. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
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References
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M¹, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A¹, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E¹, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1) Serum vitamins A and E and carotene in patients with gynecologic cancer by Heinonen PK¹, Kuoppala T, Koskinen T, Punnonen R.(PubMed)
(2) Prospective study of serum micronutrients and ovarian cancer by Helzlsouer KJ¹, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW.(PubMed)
(3) Serum alpha-tocopherol, retinol and neopterin during paclitaxel/carboplatin chemotherapy by Melichar B¹, Kalábová H, Krcmová L, Urbánek L, Hyspler R, Malírova E, Solichová D.(PubMed)
(4) Vitamin E and breast cancer by Kline K¹, Yu W, Sanders BG.(PubMed)
(5) Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA by Anderson K¹, Simmons-Menchaca M, Lawson KA, Atkinson J, Sanders BG, Kline K.(PubMed)
(6) Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer by Abouzeid AH¹, Patel NR¹, Torchilin VP²(PubMed)
(7) Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles by Fu JY¹, Blatchford DR, Tetley L, Dufès C.(PubMed)
(8) Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways by Shanker M¹, Gopalan B, Patel S, Bocangel D, Chada S, Ramesh R.(PubMed)
(9) Activation of the Fas-FasL signaling pathway by MDA-7/IL-24 kills human ovarian cancer cells by Gopalan B¹, Litvak A, Sharma S, Mhashilkar AM, Chada S, Ramesh R.(PubMed)

Ovarian cancer in vitamin A points of view

Kyle J. Norton
Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries.  It is one of most common cancer in US,  According to the national cancer institute, in 2013 Us alone, 22,240 women were diagnosed with the incidence of the disease with death of 14030.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. 
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies, linking vitamin A in reduced risk and treatment of ovarian cancer have been inclusive(a)(b)(c)(d)(e)(f).
1. Retinols
According to Temple University School of Medicine, retinols, the natural and synthetic derivatives of vitamin A, showed to inhibit the growth of human ovarian cancer cells both in vivo and in culture, suppressed ovarian carcinoma cell growth and induced apoptosis in ovarian tumor cells(1). All-trans-retinoic acid (ATRA) has shown to inhibit the growth of several ovarian tumor cell lines, other ovarian carcinoma cell lines, and its synthetic version AHPN/CD437 induced apoptosis through at least in part via an RAR(retinoic acid receptor) pathway(2)(3). Other study suggested that a novel combination of ATRA and zoledronic acid significantly induced apoptosis of related cell death in both OVCAR-3 and MDAH-2774 ovarian cancer cell lines with fewer side effects as compared to conventional cytotoxic agents(4).
 Some researchers suggested that ovarian cancer may be as a result of impaired conversion of retinol to RA in ovarian cancer cells and decreased CRBP1(Cellular Retinol Binding Protein 1) protein expression in prophylactic oophorectomies(surgery that reduces risk of breast cancer and ovarian cancer) causing concomitant losses of vitamin A metabolism and CRBP1 expression of which contribute to ovarian oncogenesis(5). Rb2/p130, a  tumor suppressor protein with function in regulation of  cell cycle progression, treatment of ATRA in sensitive ovarian carcinoma CA-OV3 cells, showed a dramatic increase in Rb2/p130 protein mediated growth arrest at G0/G1, but not growth arrest, although with a Rb2/p130 expressed at high levels in SK-OV3 cells(6)(7).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin) Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. Fenretinide (4-HPR), a synthetic retinoid, showed to induce apoptosis through a signaling cascade starting from reactive oxygen species (ROS) generation and involving endoplasmic reticulum (ER) stress response, inducing apoptosis(8) and may be used as a preventive agent in genetic mutation, such as BRCA-1 and 2 mutation carriers causes of ovarian cancer(9). According to the Medical University of Białystok, in the study of vitamin A variants in association with ovarian cancer risk, among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner on human ovary endometrioid cancer cell line CRL-11731(10). Other researchers suggested to use antioxidants, including vitamin A variants) with first-line chemotherapy in treatment for ovarian cancer. In 2 case of women with ovarian cancer treatment, antioxidants showed to improve the efficacy of chemotherapy when used in conjunction with first-line chemotherapy(11)(12).

Taking altogether, Vitamin A and its variants may be effective in reduced risk and treatment of ovarian cancer, especially when use conjunction with chemotherapy. As always, overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.  


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca

References
(a) Dietary intake and ovarian cancer risk: a systematic review by Crane TE¹, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)
(b) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(c) The role of antioxidants and vitamin A in ovarian cancer: results from the Women's Health Initiative by Thomson CA¹, Neuhouser ML, Shikany JM, Caan BJ, Monk BJ, Mossavar-Rahmani Y, Sarto G, Parker LM, Modugno F, Anderson GL.(PubMed)
(d) A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors by Paxton RJ¹, Garcia-Prieto C, Berglund M, Hernandez M, Hajek RA, Handy B, Brown J, Jones LA.(PubMed)
(e) Association of dietary vitamin A, carotenoids, and other antioxidants with the risk of ovarian cancer by Tung KH¹, Wilkens LR, Wu AH, McDuffie K, Hankin JH, Nomura AM, Kolonel LN, Goodman MT.(PubMed)
(f) Identification of carotenoids in ovarian tissue in women by Czeczuga-Semeniuk E¹, Wolczynski S.(PubMed)
(1) Retinoids and ovarian cancer byZhang D¹, Holmes WF, Wu S, Soprano DR, Soprano KJ.(PubMed)
(2) Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors by Holmes WF¹, Dawson MI, Soprano RD, Soprano KJ.(PubMed)
(3) All trans retinoic acid and cancer by Siddikuzzaman¹, Guruvayoorappan C, Berlin Grace VM.(PubMed)
(4) Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer by Karabulut B¹, Karaca B, Varol U, Muslu U, Cakar B, Atmaca H, Kisim A, Uzunoglu S, Uslu R.(PubMed)
(5) Vitamin A metabolism is impaired in human ovarian cancer by Williams SJ¹, Cvetkovic D, Hamilton TC.(PubMed)
(6) Characterization of alterations of Rb2/p130 tumor suppressor in all-trans-retinoic acid resistant SK-OV3 ovarian carcinoma cells by Fields AL¹, Soprano DR, Soprano KJ.(PubMed)
(7) Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid by Ravikumar S¹, Perez-Liz G, Del Vale L, Soprano DR, Soprano KJ.(PubMed)
(8) AF1q: a novel mediator of basal and 4-HPR-induced apoptosis in ovarian cancer cells by Tiberio P¹, Cavadini E, Callari M, Daidone MG, Appierto V(PubMed)
(9) Fenretinide (4-HPR): a preventive chance for women at genetic and familial risk? by Cazzaniga M¹, Varricchio C, Montefrancesco C, Feroce I, Guerrieri-Gonzaga A.(PubMed)
(10) Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731 by Czeczuga-Semeniuk E¹, Bielawski T, Lemancewicz D, Rusak M, Wołczyński S.(PubMed)
(11) The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer by Drisko JA¹, Chapman J, Hunter VJ.(PubMed)
(12) The use of antioxidant therapies during chemotherapy by Drisko JA¹, Chapman J, Hunter VJ.(PubMed)

Ovarian Cancer in Vitamin D Points of View

Kyle J. Norton

According to the information of national cancer institute, in 2013 Us alone. 22,240 women were diagnosed with the incidence of the disease with death of 14030.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.
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.

1. Serum of vitamin D and genes mutation
Suggestion of epidemiological studies, linking people who live in higher attitude or carry vitamin D receptor VDR rs2228570 and ApaI polymorphism are associated to the incidence of ovarian cancer and related motility rate(1)(2)(3)(4). These may be due to vitamin D deficiency and genes mutation. According to Uniwersytet Mikołaja Kopernika w Toruniu, [1.25(OH)2D3, the active form of vitamin D showed to inhibit cancer cell growth, induced cancer cell maturation, apoptosis, and decreased angiogenesis. People with lower levels of  serum 25-hydroxyvitamin D (25[OH]D) are associated to risk of ovarian cancer development(6)(7), lower overall survival rate and severe deficiency in more aggressive course of ovarian cancer(5). But the Vanderbilt University School of Medicine, in association between circulating 25(OH)D and ovarian cancer risk, in logistic regression models used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls, do not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women(8).

The efficacy
Epidemiological studies focusing in vitamin D in reduced risk of ovarian cancer have been inclusive. The study of Brigham and Women's Hospital and Harvard Medical School, in a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up, indicated no evidence to support intake of vitamin D from food or supplements or predicted 25(OH)D levels are associated to risk of ovarian cancer(9) neither Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D(10), nor vitamin D supplementation(11).  But according to Dr. Holick MF., Improved vitamin D status is associated to decreased risk for developing several deadly cancers including colon, breast, pancreatic and ovarian cancers(12) and Uniwersytet Mikołaja Kopernika w Toruniu, Vitamin D3 supplementation in moderate doses, many be benefits in decreased risk of developing cancer, including ovarian cancer(13). Some researchers suggested that 1,25-Dihydroxyvitamin D3 suppressed telomerase (a an essential enzyme that counteracts the telomere attrition accompanying DNA replication during cell division) expression and decreased in malignant human ovarian tumors as well as human ovarian cancer cell lines through microRNA(short (20-24 nt) non-coding RNAs are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs.)-498(14)(15). In ovarian epithelial cancers (OCa), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2) VD)(3) induced OCa cell apoptosis through down-regulating telomerase(16). Adding to above findings, The study by University of Hawaii Cancer Center suggested that lifetime vitamin D exposure may be inversely associated with risk of ovarian carcinoma(17).

Taking altogether, serum levels of vitamin D and vitamin D may be associated to reduced risk and treatment of  ovarian cancer, through regulation of genes and suppression telomerase expression. 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.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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References
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M¹, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A¹, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E¹, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1) Vitamin D receptor is a novel drug target for ovarian cancer treatment by Zhang X¹, Nicosia SV, Bai W.(PubMed)
(2) Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk by Xu Y¹, He B, Pan Y, Deng Q, Sun H, Li R, Gao T, Song G, Wang S.(PubMed)
(3) Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium by Lurie G¹, Wilkens LR, Thompson PJ, Carney ME, Palmieri RT, Pharoah PD, Song H, Hogdall E, Kjaer SK, DiCioccio RA, McGuire V, Whittemore AS, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Goodman MT; Ovarian Cancer Association Consortium.(PubMed)
(4) Vitamin D receptor FokI, BsmI, ApaI, and TaqI polymorphisms and susceptibility to ovarian cancer: a meta-analysis by Song GG¹, Lee YH.(PubMed)
(5) [The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

[Article in Polish by Walentowicz-Sadłecka M¹, Sadłecki P, Walentowicz P, Grabiec M.(PubMed)

(6) Casting light on 25-hydroxyvitamin D deficiency in ovarian cancer: a study from the NHANES by Bakhru A¹, Mallinger JB, Buckanovich RJ, Griggs JJ.(PubMed)
(7) Serum 25-hydroxyvitamin D and the risk of ovarian cancer by Toriola AT¹, Surcel HM, Agborsangaya C, Grankvist K, Tuohimaa P, Toniolo P, Lukanova A, Pukkala E, Lehtinen M.(PubMed)

(8) Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers by Zheng W¹, Danforth KN, Tworoger SS, Goodman MT, Arslan AA, Patel AV, McCullough ML, Weinstein SJ, Kolonel LN, Purdue MP, Shu XO, Snyder K, Steplowski E, Visvanathan K, Yu K, Zeleniuch-Jacquotte A, Gao YT, Hankinson SE, Harvey C, Hayes RB, Henderson BE, Horst RL, Helzlsouer KJ.(PubMed)
(9) Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies by Prescott J¹, Bertrand KA, Poole EM, Rosner BA, Tworoger SS.(PubMed)
(10) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer by Tworoger SS¹, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE.(PubMed)
(11) The association of vitamin D supplementation with the risk of cancer in postmenopausal women by Redaniel MT¹, Gardner MP, Martin RM, Jeffreys M.(PubMed)
(12) Vitamin D, sunlight and cancer connection by Holick MF.(PubMed)
(13) [The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

[Article in Polish] by Walentowicz-Sadłecka M¹, Sadłecki P, Walentowicz P, Grabiec M.(PubMed)

(14) MIR498 microRNA 498 [ Homo sapiens (human) ](PubMed)

(15) 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498 by Kasiappan R¹, Shen Z, Tse AK, Jinwal U, Tang J, Lungchukiet P, Sun Y, Kruk P, Nicosia SV, Zhang X, Bai W.(PubMed) 

(16) Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase by Jiang F¹, Bao J, Li P, Nicosia SV, Bai W.(PubMed) 

(17) Cataract and ovarian carcinoma: is the vitamin D hypothesis alive? by Lurie G¹, Matsuno RK, Wilkens LR, Thompson PJ, Ollberding NJ, Carney ME, Goodman MT.(PubMed)