Ovarian Cancer in Vitamin C Points of View

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 information of national cancer institute, in 2013 Us alone 22,240 women were diagnosed with the incidence of the disease with death of 14030.
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 conflict results
Epidemiological studies, linking vitamin C in reduced risk of endometrial cancer have produced inconsistent results. The Robert Wood Johnson Medical School study, indicated a little evidence of an association with dietary TAC or the others individual antioxidants, including vitamin C in reduced risk of epithelial ovarian cancer(1) But the University of Kansas Medical Center, showed a positive effects of vitamin C in inhibition and death in ovarian cancer cells. through multiple pathways. Composition of vitamin C and the conventional chemotherapeutic agents carboplatin, synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer(2) and  AA at ≥250 μmol/L showed to completely inhibit serum-stimulated cell proliferation in all cell lines tested, including IOSE-385, OVCAR-3, and OVCA-432 which were was partially (∼10%-20%) countered by E2β and its metabolites(3). Other researchers suggested that ascorbic acid at the normal plasma concentration has an essential role in maintaining the NK cytotoxicity against ovarian cancer cells in mouse model and depletion of ascorbic acid may impair NK cell activity(4).

The effects
Arsenic trioxide (As2O3), a novel compound generated from the oxidation of arsenic routinely, and pharmacological doses of Ascorbic acid(AA), showed to inhibited ovarian cancer cells through manipulation of cellular glutathione (GSH) levels via enhancement of AA's cytotoxicit. These result indicated that depletion of GSH may promote the progression of the disease(5).In  in mice bearing glioblastoma xenograft, oral ascorbate administration, exhibited the production of sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood and significantly decreased growth rates of ovarian cancer(6). In human ovarian cancer cell line SK-OV-3, the composition of lysine, proline, arginine, ascorbic acid and green tea extract inhibited the cancer development and invasion, possibly through MMP expression(7). According to American University of the Caribbean, combined treatments of  VC (ascorbic acid), VK3 (menadione) on the cellular and nuclear morphology and DNA content of a human ovarian carcinoma cell line (MDAH 2774), showed to inhibit the cancer cell line through generalized DNA degradation(8)(9).

Taking altogether, Vitamin C and its composition may b4 effective in reduced risk and treatment of ovarian cancer through activation of its antioxidant cytotoxicity in enhancement the effectiveness of either novel agents or chemical compounds. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

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) Total and individual antioxidant intake and risk of epithelial ovarian cancer by Gifkins D¹, Olson SH, Paddock L, King M, Demissie K, Lu SE, Kong AN, Rodriguez-Rodriguez L, Bandera EV.(PubMed)
(2) High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy by Ma Y¹, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q.(PubMed)
(3) Estradiol 17β and its metabolites stimulate cell proliferation and antagonize ascorbic acid-suppressed cell proliferation in human ovarian cancer cells by Li HH¹, Zhao YJ, Li Y, Dai CF, Jobe SO, Yang XS, Li XF, Patankar MS, Magness RR, Zheng J.(PubMed)
(4) Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model.

Kim JE¹, Cho HS, Yang HS, Jung DJ, Hong SW, Hung CF, Lee WJ, Kim D.(PubMed)

(5) Differential augmentative effects of buthionine sulfoximine and ascorbic acid in As2O3-induced ovarian cancer cell death: oxidative stress-independent and -dependent cytotoxic potentiation by Ong PS¹, Chan SY, Ho PC.(PubMed)
(6) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice by Chen Q¹, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M.(PubMed)
(7) Inhibition of matrix metalloproteinase-2 secretion and invasion by human ovarian cancer cell line SK-OV-3 with lysine, proline, arginine, ascorbic acid and green tea extract by Roomi MW¹, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M.(PubMed)
(8) 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)



(9) 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 Herbs Points of View

 Kyle J. Norton (Draft Article)

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 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 herbs have showed to inhibit the progression of cancer with little or no side effects.

1. Licorice
Licorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc. Isoliquiritigenin (ISL), a licorice chalconoid, induced apoptosis in ovarian carcinoma SKOV-3 cells and increased intracellular ROS levels through ER stress-triggered signaling pathways, according to Shihezi University(1). 18β-glycyrrhetinic acid, another compound found in the same herb, potentiated the effective ness of Hsp90(heat shock protein 90) in induced apoptosis-related protein activation, nuclear damage, and cell death, through the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated cell death pathway(2). Licochalocone , a natural phenol licorice compounds, enhanced 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a anticancer drugs, in exhibition of apoptosis in human epithelial ovarian carcinoma OVCAR-3 and SK-OV-3 cell lines, through decreased pro proliferative and increased apoptotic protein expression(3).

2. Cascara sagrada
Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.
Emodin, a chemical compound found in the herb, inhibited  drug resistant ovarian tumor growth through increasing cellular concentration of anti cancer drug paclitaxel and re-sensitizing the resistant cells to paclitaxel(4). The study of the effect of tamoxifen, emodin, and plumbagin in BRCA1-blocked ER-positive BG-1 ovarian cancer cells inhibited ovarian cancer cell line through a induced loss of mitochondrial membrane potential (DeltaPsi(m)), nuclear condensation, DNA fragmentation, and morphological changes(5). In human ovarian carcinoma HO-8910PM cell lines, emodin and apigenin, induced cytotoxicity on HO-8910PM cells, through inhibition of tumor invasion and metastasis(6).

3. Aloe vera
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Aloe-emodin, a major compound of herbal Aloe Vera, in composition with Reih exhibited anti  human ovarian cancer SK-OV-3, effect in half inhibitory concentration (IC50)(7). Aloe-emodin (AE) alone, showed the effective in significant inhibition of  invasion, migration, and adhesion capacities of HO-8910PM cells(8). Aloin, a natural anthraquinone, extract from Aloe Vera, did not inhibit initiation of DNA synthesis and  cells replicated a full complement of DNA but had difficulty in M phase of cell cycle(9).

4. 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(10). In Human epithelial ovarian cancer cell line A2780, S-allylcysteine (SAC), , an antioxidant and chemical compound extracted from garlic, SAC  induced apoptosis through G1/S phase arrest by decreased the proliferative expression and increased expression of active of pro apoptosis(11). In human ovarian cancer cell lines, SAC and SAMC induced apoptosis through activation of E-cadherin(12).

5. Ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root). ginsenoside Rg3, a major chemical compound found in Ginseng, inhibited of SKOV-3 cell line through inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9(13).
In composition of ginsenoside Rg3 and cyclophosphamide CTX, the  combination significantly inhibited growth and angiogenesis of ovarian cancer(14). Ginsenoside Rh2, another chemical compound of the herb, inhibited the cancer cells through induction of apoptosis in addition to augmentation of the natural killer activity in spleen cells from tumor-hearing nude mice(15).  

6. Lingzhi (LZ)
Ling Zhi is also known as Lucid Ganoderma. The sweet and netral herb has been used in TCM to treat cough, asthma, tinnitus, deafness and lassitude of the loins and knees, palpitation, insomnia and amnesia, hepatitis B, etc. as it nourishes Yin and Blood, strengthens the Spleen tonifies Qi and Body Fluids, calms the Mind, strengthens the Stomach, etc., by enhancing the functions of Lung, Kidney, Liver, Heart, Spleen and Stomach channels.
Lingzhi (LZ),  also known as Ganoderma lucidum, inhibited the ovarian cancer cell line OVCAR-3, through  suppressing cell growth and inducing antioxidative/detoxification activity(16). Other study suggested that LingZhi also strongly decreased cell numbers in a dose-dependent manner. through inhibition of colony formation, cell migration and spheroid formation(17).

7. Cranberry
Cranberry is a evergreen dwarf shrubs, genus Vaccinium, belonging to the family  Ericaceae, native to Northern America and Southern Asia. Because of health benefits, it has been cultivated in some parts of the world forcommercial profits and used in traditional and herbal medicine to treat wounds,urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems.
Proanthocyanidin (PAC)-rich isolate from cranberry (PAC-1), inhibited ovarian cancer SKOV-3 cell line through blocked cell cycle progression through the G2/M phase, increased the generation of reactive oxygen species (ROS), and induced apoptosis through activation of intrinsic and extrinsic pathway components(18). Treatment with Proanthocyanidin in SKOV-3 ovarian cancer cells  exhibited classic apoptotic changesnd pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value(19).

8. Rosemary
Rosemaryis a perennial herb with fragrant, evergreen, needle-like leaves, the genus Rosmarinus, belonging to the family Lamiaceae. Its fresh and dried leaves has been used frequently in traditional Mediterranean cuisine and as flavor foods while barbecuing. Rosnary has been used in traditional medicine as an antiseptic, antioxidant, and antispasmodic agent to treat circulatory problem, eczema, rheumatism, muscle pain, etc.
Crude extracts of rosemary (Rosmarinus officinalis L), has been found to consist anti-proliferative property on several human cancer cell lines and antioxidant and anti-inflammatory properties(20).
Carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA), the main ingredients in rosemary extract, exhibited the significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration)(21).

9. Devil's Club 
Devil's Club is a large shrub, genus Oplopanax, belonging to the family Aralioideae, native to the cool moist forests of western North America. The herb has been used in traditional and herbal medicine as Adaptogen, Antipyretic, Pain Reliever, Antitussive, Antibacterial agent and to treat Arthritis, Diabetes, Colds, Cough, Sore throat, Chest congestion, Stomach pain, Constipation, Gall stones, Influenza, Cancer, etc.
Ethanolic extract of Devil club dry root bark powder, showed to inhibit the proliferation of some cancer cell lines including K562, HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50))(22). Water, 70% ethanol, 100% ethanol, and ethyl acetate extracts of OH exhibited significant anti-proliferation effect against both cisplatin sensitive and resistant human ovarian cell lines, including human ovarian cancer cell lines A2780, A2780CP70, OVCAR3, and OVCAR10, according the University of British Columbia(23). In comparison with stem and berry, researchers found that stem extract after administration of 72 h, increased cells apoptosis cells through cell cycle arrest and induction of apoptosis on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC)(24).

10. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgolide B (GB), a major component of Ginkgo biloba extracts, significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells with treatment of with 100 µM GB for 3 days, through the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1(25). In BRCA1 mutations risk of developing ovarian cancers, bioinformatics software analysis indicated that GB treatment involved multiple mechanisms and signal pathways in anticancer activities in BRCA1-mutant cells(26). According to Harvard Medical School, in vitro experiments, Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in normal and ovarian cancer cells(27).

11. Grape seed extract
Grape Seed Extract is the commercial extracts from whole grape seeds that contains many concentrations, including Resveratrol, vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc..The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc.
Resveratrol, a major compound found in grape seed extract showed to prevent Cisplatin-induced EMT in ovarian cancer cells, through increased cell death, and reduced the risk of metastasis(28). The
University of Michigan, in the study the effects of Resveratrol in response of ovarian cancer cells, indicated that inhibited growth and induced death in a panel of five human ovarian carcinoma cell lines, associated with mitochondrial release of cytochrome c, formation of the apoptosome complex, and caspase activation(29). The Seoul National University suggested that Resveratrol retarded the growth of PA-1 cell xenograft and the expression of eEF1A2 (the gene may be critical in the development of ovarian cancer) in athymic nude mice(30).

12. Valerian is a perennial flowering plant, in the genus Valeriana, belonging to the family Valerianaceae, native to Europe and parts of Asia. The herb has been used as a sedative and relaxing agent and to treat the liver, the urinary tract, the digestive tract problem, nerve conditions, etc.
IVHD-valtrate, one of the most active Valeriana jatamansi or Indian Valerian derivatives, inhibited the growth and proliferation of the A2780 and OVCAR-3 ovarian cancer cell lines, through  G2/M phase arrest and induced apoptosis, and significantly suppressed the growth of A2780 and OVCAR3 xenograft tumors in a dose-dependent manner(31). 

13. Phyllanthus niruri L. 
Phyllanthus niruri L., also known as stonebreaker or seed-under-leaf, is a widespread tropical plant the genus Phyllanthus, belonging to the family Phyllanthaceae, native to to China, India and South/Central America. The herb has been used in folk medicine to treat kidney stones and in Indian medicine which is for problems of the stomach, genitourinary system, liver, kidney and spleen(32).
Corilagin, a major chemical constituent from Phyllanthus niruri L., inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey associated with cell cycle arrest at the G2/M stage and enhanced apoptosis(33). Other researchers suggested that Corilagin inhibited into the culture supernatant of all tested ovarian cancer cell lines through blocking the secretion of TGF-β(34).

15. Thelypteris torresiana (Gaud) 
Thelypteris torresiana (Gaud)  is a species of fernin the genus of Thelypteris, belonging to the family Thelypteridaceae native to China. The herb has been used in traditional Chinese medicine for treatment of treatment of hydropsy and traumatic bleeding (Institute of Botany, 1976; Ding, 1982).
The total flavonoid fraction from the roots of M. torresiana shows significant antitumor activity(35).
Protoapigenone, a novel flavonoid isolated from the whole plant Thelypteris torresiana (Gaud), exhibited a significant cytotoxicity on human ovarian cancer cells MDAH-2774 and SKOV3 but not on the immortalized non-cancer ovarian epithelial cells HOSE 6-3 and HOSE 11-12, through S and G2/M phases arrest via decreasing the expression of p-Cdk2, Cdk2, p-Cyclin B1 and Cyclin B1(activity is restricted to the G1-S phase, and is essential for cell cycle G1/S phase transition. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B)(36)), as well as increasing the expression of inactive p-Cdc25C(antibody)(37).

Taking altogether, Certain herbs have found effectively in reduced risk and treatment of ovarian cancer, through cels cycle arrest, up and down regulation of some mechanisms, but large sample size and multi centers studies are necessary to validate the effectiveness of principle ingredients. As always, All articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve 
Optimal Health And Loose Weight

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) 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) Involvement of endoplasmic reticulum stress in isoliquiritigenin-induced SKOV-3 cell apoptosis by Yuan X¹, Yu B, Wang Y, Jiang J, Liu L, Zhao H, Qi W, Zheng Q.(PubMed)
(2) 18β-glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathway by Yang JC¹, Myung SC, Kim W, Lee CS(PubMed)
(3) Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways by Lee CS¹, Kwak SW, Kim YJ, Lee SA, Park ES, Myung SC, Kim W, Lee MS, Lee JJ.(PubMed)
(4) Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro by Li J¹, Liu P, Mao H, Wanga A, Zhang X.(PubMed)
(5) Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen in BG-1 ovarian cancer cells by Srinivas G¹, Annab LA, Gopinath G, Banerji A, Srinivas P.(PubMed)
(6) [Effect of emodin and apigenin on invasion of human ovarian carcinoma HO-8910PM cells in vitro].[Article in Chinese] by Zhu F¹, Liu XG, Liang NC.(PubMed)
(7) Synthesis and anti-tumor activity evaluation of rhein-aloe emodin hybrid molecule by Yuan YF¹, Hu XY, He Y, Deng JG.(PubMed)
(8) Inhibitory effect of aloe-emodin on metastasis potential in HO-8910PM cell line by He TP¹, Yan WH, Mo LE, Liang NC.(PubMed)
(9) DNA ploidy and S phase fraction of breast and ovarian tumor cells treated with a natural anthracycline analog (aloin) by Esmat AY¹, El-Gerzawy SM, Rafaat A.(PubMed)
(10) 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)
(11) S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro by Xu YS¹, Feng JG², Zhang D³, Zhang B⁴, Luo M³, Su D⁵, Lin NM(PubMed)
(11) A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression by Chu Q¹, Ling MT, Feng H, Cheung HW, Tsao SW, Wang X, Wong YC.(PubMed)
(12) Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe by Kim JS¹, Lee SI, Park HW, Yang JH, Shin TY, Kim YC, Baek NI, Kim SH, Choi SU, Kwon BM, Leem KH, Jung MY, Kim DK.(PubMed)
(13) Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis by Xu TM¹, Cui MH, Xin Y, Gu LP, Jiang X, Su MM, Wang DD, Wang WJ.(PubMed)
(14) Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer by Xu TM¹, Xin Y, Cui MH, Jiang X, Gu LP.(PubMed)
(15) Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells by Nakata H¹, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, Kudoh K, Nagata I, Shinomiya N.(PubMed)
(16) Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3 by Hsieh TC¹, Wu JM.(PubMed)
(17) Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin by Zhao S¹, Ye G, Fu G, Cheng JX, Yang BB, Peng C.(PubMed)
(18) Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells by Kim KK¹, Singh AP, Singh RK, Demartino A, Brard L, Vorsa N, Lange TS, Moore RG.(PubMed)
(19) Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin by Singh AP¹, Singh RK, Kim KK, Satyan KS, Nussbaum R, Torres M, Brard L, Vorsa N.(PubMed)
(20) Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis.by Cheung S¹, Tai J.(PubMed)
(21) Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro by Tai J¹, Cheung S, Wu M, Hasman D.(PubMed)
(22) In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax horridus by Tai J¹, Cheung S, Cheah S, Chan E, Hasman D.(PubMed)
(23) Inhibition of human ovarian cancer cell lines by devil's club Oplopanax horridus by Tai J¹, Cheung S, Chan E, Hasman D.(PubMed)
(24) High performance liquid chromatographic analysis and anticancer potential of Oplopanax horridus: comparison of stem and berry extracts by Wang CZ¹, Aung HH, Mehendale SR, Shoyama Y, Yuan CS.(PubMed)
(25) Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells by Jiang W¹, Cong Q, Wang Y, Ye B, Xu C.(PubMed)
(26) Ginkgo may prevent genetic-associated ovarian cancer risk: multiple biomarkers and anticancer pathways induced by ginkgolide B in BRCA1-mutant ovarian epithelial cells by Jiang W¹, Qiu W, Wang Y, Cong Q, Edwards D, Ye B, Xu C.(PubMed)
(27) Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence by Ye B¹, Aponte M, Dai Y, Li L, Ho MC, Vitonis A, Edwards D, Huang TN, Cramer DW.(PubMed)
(28) Resveratrol Inhibits Cisplatin-Induced Epithelial-to-Mesenchymal Transition in Ovarian Cancer Cell Lines by Baribeau S, Chaudhry P, Parent S, Asselin E.(PubMed)
(29) Resveratrol-induced autophagocytosis in ovarian cancer cells by Opipari AW Jr¹, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR.(PubMed)
(30) Resveratrol suppresses growth of human ovarian cancer cells in culture and in a murine xenograft model: eukaryotic elongation factor 1A2 as a potential target by Lee MH¹, Choi BY, Kundu JK, Shin YK, Na HK, Surh YJ.(PubMed)
(31) Valeriana jatamansi constituent IVHD-valtrate as a novel therapeutic agent to human ovarian cancer: in vitro and in vivo activities and mechanisms.

Li X¹, Chen T, Lin S, Zhao J, Chen P, Ba Q, Guo H, Liu Y, Li J, Chu R, Shan L, Zhang W, Wang H.(PubMed)

(32) "Keelanelli". Tamilnadu.com. 21 January 2013.

(33) A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways by Jia L¹, Jin H, Zhou J, Chen L, Lu Y, Ming Y, Yu Y.(PubMed)

(34) A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways by Jia L¹, Jin H, Zhou J, Chen L, Lu Y, Ming Y, Yu Y.(PubMed) 

(35) In vitro and in vivo antitumor activity of Macrothelypteris torresiana and its acute/subacute oral toxicity by Huang XH¹, Xiong PC, Xiong CM, Cai YL, Wei AH, Wang JP, Liang XF, Ruan JL(PubMed) 

(36) Bioworld

(37) Protoapigenone, a novel flavonoid, inhibits ovarian cancer cell growth in vitro and in vivo by Chang HL¹, Su JH, Yeh YT, Lee YC, Chen HM, Wu YC, Yuan SS.(PubMed)

Polycystic kidney disease in Foods' Points of View

Polycystic kidney disease, also known as polycystic kidney syndrome is a cystic genetic disorder(a)(b)(c) of the kidneys, classified into:
A. Autosomal dominant polycystic kidney disease (ADPKD) affects all ethnic groups with a prevalence of 1:400-1:1000 live births. The disease induced formation of  numerous cysts in the kidneys with progressively expand and eventually destroy normal kidney structure and function. and may be associated to other disease complications(1)
B. Autosomal recessive polycystic kidney disease (ARPKD) is genetic disorder due to mutation of gene in chromosomal locus 6p12.2., causing up to 50% of affected neonates die of pulmonary hypoplasia and specific changes in the kidney and liver. Children who survive neonatal period (from birth to 28 days of age)may be experience with decrease in kidney size (not affect the kidney function) and change in echogenicity occurs, producing a pattern similar to patients with autosomal dominant polycystic kidney disease(2).
Although the disease is due to gene mutation, according to the study by the West Virginia University, certain phytochemicals in foods and herbs have found effectively in attenuation of cyst pathogenesis in animal studies(3).

1. Dietary Flax seeds
Flax is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, it can grow to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad. According to the study by the University of Manitoba, Han:SPRD-cy rats fed flaxseed, showed to preserve renal function and reduce histologic injury, through tissue retention of succinate and betaine which may have a metabolic role in the reduction of chronic renal injury(4). Other study suggested that flax seed diet alters renal content of polyunsaturated fatty acids and promotes the formation of less inflammatory classes of renal prostanoides(5).

2. 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.
Soy protein may be effective in slow progression of renal injury in the Han:SPRD-cy rat, according to the study by theUniversity of Manitoba. The study with Han:SPRD-cy rat, fed with soy protein diet showed to associate with reduced cystic change, epithelial cell proliferation, macrophage infiltration  and fibrosis and prevented a significant elevation in serum creatinine in diseased versus normal animals(6). In Normal (+/+) and affected (cy/+) weanling male and female Han:SPRD-cy rats, soy protein is found to lower IGF-I in +/+ animals, of that supported a role for IGF-I in the pathogenesis of disease in the Han:SPRD-cy rat and an ameliorating role for dietary soy protein(7). Other researchers suggested that isocaloric diets based on 20% casein or 20% heat-treated soy protein at weaning ad libitum for 8 wk, showed a significant effect in  lower serum creatinine (66 vs. 125 mumol/l; P = 0.002), lower urinary ammonium excretion (0.080 vs. 0.173 mmol/kg; P = 0.01), reduced renal cysts, renal fibrosis, macrophage infiltration, renal tubular cell proliferation, and apoptosis(8)

3. Dietary conjugated linoleic acid
Dietary conjugated linoleic acid(CLA) derived from ruminants, found abundantly in diary produces and meats. In  Han:SPRD-cy rat model of polycystic kidney disease (PKD) fed with CLA, showed an reduction of renal production of PGE2, without reduced availability of the precursor fatty acid, AA. Short-term feeding also exhibited significant renal anti-inflammatory and antifibrotic effects(9). Other in the study of Male and female offspring of Han:SPRD-cy heterozygotes fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks, showed that both CLA diets reduced body fat content in both genders but did not change lean body mass, renal cystic change in female, fibrosis, macrophage infiltration, tissue oxidized LDL content and proliferation of epithelial cells. The study also found significantly increase of serum creatinine in female rat. and with a  significant negative correlation with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects(10).

4. Fish oil
Fish oil containing a large amounts of omega-3 fatty acids may be associated to reduced risk of Polycystic kidney disease.Dietary fish oil (FO) and soy protein (SP) was found to slow Polycystic kidney disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD), with fish oil through inhibition of both COX and LOX products produced from n-6 fatty acids and increased 3-series prostanoids in both normal and diseased cortex and medulla(11). The Royal Brisbane and Women's Hospital, Brisbane, study showed a potential benefits of omega-3 polyunsaturated fatty acids on the progression of kidney disease and patient survival, as the acids decrease blood pressure, a known accelerant of kidney disease progression(12). But the study at the Kyorin University School of Medicine indicated that Eicosapentaenoic acids (EPA), one of omega3-polyunsaturated fatty acids, show no significant benefits in the testing of non-azotemic patients(13).

Taking altogether, the above list has been found effectively in reduced the progression of inherited Polycystic kidney disease through many different mechanisms. Further studies are necessary to validate its effectiveness. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve
Optimal Health And Loose Weight

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

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References
(a) Loss of Polycystin-1 Inhibits Bicc1 Expression during Mouse Development by Lian P¹, Li A¹, Li Y², Liu H², Liang D³, Hu B³, Lin D⁴, Jiang T⁵, Moeckel G⁶, Qin D⁷, Wu G⁸.(PubMed)
(b) Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations by Freedman BS¹, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV.(PubMed)
(c) Polycystin-1 but not polycystin-2 deficiency causes upregulation of the mTOR pathway and can be synergistically targeted with rapamycin and metformin by Mekahli D¹, Decuypere JP, Sammels E, Welkenhuyzen K, Schoeber J, Audrezet MP, Corvelyn A, Dechênes G, Ong AC, Wilmer MJ, van den Heuvel L, Bultynck G, Parys JB, Missiaen L, Levtchenko E, De Smedt H.(PubMed)
(1) Metabolic abnormalities in autosomal dominant polycystic kidney disease by Mao Z¹, Xie G, Ong AC.(PubMed)
(2)  decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease by Blickman JG¹, Bramson RT, Herrin JT.(PubMed)
(3) Evidence for a role of proteins, lipids, and phytochemicals in the prevention of polycystic kidney disease progression and severity by Maditz KH¹, Gigliotti JC, Tou JC.(PubMed)
(4) The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease by Ogborn MR¹, Nitschmann E, Bankovic-Calic N, Buist R, Peeling J(PubMed)
(5) [Effect of a modified low protein and low fat diet on histologic changes and metabolism in kidneys in an experimental model of polycystic kidney disease].[Article in Serbian] by Banković-Calić N¹, Ogbori MR, Nicman E.(PubMed)
(6) Modification of polycystic kidney disease and fatty acid status by soy protein diet by Ogborn MR¹, Nitschmann E, Weiler HA, Bankovic-Calic N.(PubMed)
(7) Dietary soy protein effects on disease and IGF-I in male and female Han:SPRD-cy rats by Aukema HM¹, Housini I.(PubMed)
(8) Soy protein modification of rat polycystic kidney disease by Ogborn MR¹, Bankovic-Calic N, Shoesmith C, Buist R, Peeling J.(PubMed)
(9) Dietary conjugated linoleic acid reduces PGE2 release and interstitial injury in rat polycystic kidney disease by Ogborn MR¹, Nitschmann E, Bankovic-Calic N, Weiler HA, Fitzpatrick-Wong S, Aukema HM.(PubMed)
(10) Dietary conjugated linoleic acid renal benefits and possible toxicity vary with isomer, dose and gender in rat polycystic kidney disease by Ogborn MR¹, Nitschmann E, Goldberg A, Bankovic-Calic N, Weiler HA, Aukema HM.(PubMed)
(11) Renal cyclooxygenase and lipoxygenase products are altered in polycystic kidneys and by dietary soy protein and fish oil treatment in the Han:SPRD-Cy rat by Ibrahim NH¹, Jia Y, Devassy JG, Yamaguchi T, Aukema HM.(PubMed)
(12) Omega-3 polyunsaturated fatty acids in the treatment of kidney disease by Fassett RG¹, Gobe GC, Peake JM, Coombes JS.(PubMed)
(13) he effect of eicosapentaenoic acid on renal function and volume in patients with ADPKD by Higashihara E¹, Nutahara K, Horie S, Muto S, Hosoya T, Hanaoka K, Tuchiya K, Kamura K, Takaichi K, Ubara Y, Itomura M, Hamazaki T.(PubMed)

Ovarian Cancer in Foods Points of View

Kyle J. Norton (Draft Article)

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 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 foods have showed to inhibit the progression of cancer with little or no side effects.

1. Cruciferous vegetables Cruciferous vegetables are the group of  vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc. A meta-analysis of observational studies in reviews of a total of 4,306 cases in 375,562 controls in 11 independent studies indicated a positive effect of consumption of Cruciferous vegetables in a reduced risk of ovarian cancer in case-control studies(1). Isothiocyanates, antioxidants and chemical constituent in cruciferous vegetable, inhibit the cell viability of human ovarian cancer cells, through improved antioxidant status(2). sulforaphane, SFN the active compound in  Isothiocyanates, inhibited the human ovarian cancer cell lines through down-regulate Bcl-2 (a gene involved in anti-apoptosis) protein levels in both cell types and up- regulate the cleaved poly(ADP-ribose) polymerase (PARP) after 6 days of treatment(3). In  cell lines MDAH 2774 and SkOV-3 with an IC50, SFN exhibited the suppression of growth in a a dose-dependent manner by reduced cell migration and increased apoptotic cell death(4).

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(5). In Human epithelial ovarian cancer cell line A2780, S-allylcysteine (SAC), , an antioxidant and chemical compound extracted from garlic, SAC  induced apoptosis through G1/S phase arrest by decreased the proliferative expression and increased expression of active of pro apoptosis(6). In human ovarian cancer cell lines, SAC and SAMC induced apoptosis through activation of E-cadherin(7).

3. Ginger
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc. 6-shogaol, achmeical constituent isolated from ginger showed to inhibited cell growth and modulated secretion of angiogenic factors in ovarian cancer cells, through activation of NF-kappaB and and production of VEGF(stimulation of vasculogenesis and angiogenesis) and IL-8(Interleukin 8, a chemokine of the immune system)(8). In human A549, SK-OV-3, SK-MEL-2, HCT15 tumor cells and the transgenic mouse ovarian cancer cell lines, 6-shogaol exhibited the most potent cytotoxicity against cell proliferation(9).

4. Curcumin
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in trditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
Curcumin, a major chemical compound found in turmeric, inhibited the proliferation of both cisplatin-resistant (CR) and sensitive (CS) human ovarian cancer cells through cell cycle arrest, by enhancing the p53 phosphorylation and apoptosis through the activation of caspase-3 followed by PARP degradation(10). E24, a novel curcumin analog, in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells, in  time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis(11). The Dalhousie University study also showed a positive effect of curcumin in inhibition of ovarian cancer cell lines independently to p53 but involves p38 MAPK activation, ablation of prosurvival Akt signaling(role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration), and reduced expression of the antiapoptotic proteins Bcl-2 and surviving((baculoviral inhibitor)(12).

5. 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.
In the study conduced by Brigham and Women's Hospital, lycopene found abundantly in tomato iintake is inversely associated to risk of ovarian cancer, predominantly in premenopausal women(13). and the Loma Linda University study also showed a significantly reduced risk of all ovarian cancer with higher tomato consumption in comparing intakes > or = five times/week versus never to < 1 time/week(14). But the reviews from FDA's  of the scientific data for tomato and/or lycopene intake with respect to risk reduction for certain forms of cancer, found very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers(15).

6. Red wine
Red wine made from anthocyan pigments of the skin of the grape
Resveratrol (trans-3,4',5-trihydroxystilbene; RES), a phytoestrogen, exists in grape skin and red wine showed to inhibited on estrogen-dependent ovarian cancer cells  proliferation, through cell cycle arrest at the G1 phase and increased the expression of p21(16). Other researchers suggested that a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days exhibited effectively in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells(17). The University of Michigan study indicated the effectiveness of  Resveratrol (3,5,4-trihydroxystilbene) in inhibited growth and induced death in a panel of five human ovarian carcinoma cell lines, through association with mitochondrial release of cytochrome c, formation of the apoptosome complex, and caspase activation(18).

7. 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.
Genistein(7-difluoromethoxyl-5,4'-di-n-octyl ), as a major isoflavonoid isolated from dietary soybean, inhibited ovarian cancer cell growth and migration, through down-regulated miR-27a expression and significantly increased expression of Sprouty2, a putative miR-27a target gene(19). On bisphenol A (BPA) or 17β-estradiol (E2)-induced cell growth and gene alterations of BG-1 ovarian cancer cells expressing estrogen receptors (ERs), GEN(Glycine) effectively suppressed BG-1 cell proliferation promoted by E2 or BPA throuh inhibiting cell cycle progression and decreased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition(20). The First Affiliated Hospital of Guangzhou Medical college, the derivative 7-difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG), a novel synthetic genistein, was more potent by exerting strongest activity against CoC1 and SKOV3 cells through cell cycle arrest in the G2/M phase and exhibited apoptotic cell death with concomitant attenuation of Forkhead box protein M1 (FoxM1)(a transcriptional activator involved in cell proliferation.)(21).

8. Olive oil
Olive is belongs to 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.
Accumulations of evidence suggested that Olive oil, an integral ingredient of the "Mediterranean diet" may play an important role  in lowering the risk of several types of cancer, including ovarian cancer, through suppressesion of HER2 at the transcriptional level by up-regulating the expression of the Ets protein PEA3 -a DNA-binding protein that specifically blocks HER2 promoter activity- in ovarian cancer cell lines(22). Data from a multicentre case-control study conducted between 1992 and 1999 in Italy, indicated a protective effect of olive oil against ovarian cancer in this Italian population(23). Oleic acid, the main olive oil's monounsaturated fatty acid, showed to suppress the overexpression of HER2 (erbB-2), a well know nutation gene in expression of invasive progression and metastasis in several human cancers, including ovarian cancer(24). Recent study conducted in China also reported that green tea consumption reduced risk of ovarian cancer and increased survival post diagnosis(26).

9. 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. 
"Green tea consumption suggested to enhance the survival of epithelial ovarian cancer", the cohort comprised 254 patients recruited during 1999-2000 with histopathologically confirmed epithelial ovarian cancer and followed up for a minimum of 3 years said, out of 254, 81 (77.9%) of 104 tea-drinkers who survived to the time of interview, compared to only 67 women (47.9%) still alive among the 140 non-drinkers(27). Epigallocatechin‑3‑gallate, phytochemical found in green tea EGCG significantly inhibited the proliferation of OVCAR‑3 cells in a time‑ and concentration‑dependent manner, through increased expression of the activity of p38/MAPK( control of stemness of glioma-initiating cells) and downregulation of the protein expression of MMP2(usually seen in invasive and highly tumorigenic cancers)(28). The study of combination of Epigallocatechin gallate and sulforaphane against paclitaxel-resistant ovarian cancer cells, showed to induced apoptosis of paclitaxel-resistant ovarian cancer cell lines through down-regulating of hTERT(Telomerase reverse transcriptase allows senescent cells that would otherwise become postmitotic and undergo apoptosis) and Bcl-2 and promote DNA damage response(29).


10. Rice bran
Rice bran contains layer between the inner white rice grain and the outer hull. Phytic acid (PA) isolated rice bran induced marked growth inhibition in ovary, with 50% growth inhibition concentration (IC50)(30).In methanolic extracts from Njavara rice bran, showed to exhibit its anti-proliferative property in C6 glioma cells, possibly through superior antioxidant activity as evidenced by scavenging of free radicals including DPPH and NO(31).

12. Avocado
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceae.
Omega-6 polyunsaturated (n-6) fatty acids found in avocado inhibited the proliferation of ovarian cancer cell(32).

13. Fatty Fish
Fatty fish containing a large amounts of omega-3 fatty acids may be associated to reduced risk of ovarian cancer. High fish intake may be associated with a significantly reduced risk in the 2 case-control studies(33). The Southern Illinois University Carbondale, in hen study indicated that 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries. may be an effective approach in preventing ovarian carcinogenesis(34).   

14. Flaxseed
Flax seed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, it can grow to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad. Omega-3 fatty acids (OM-3FAs) found in flaxseed, showed statistically significant inhibitory effect under the influence of OM-3FAs was detected in all four cell lines, (SKOV-3 [p53 null], TOV-21G [wt p53] and OVCAR-3 [mutant p53]) and one immortalized ovarian surface epithelial cell line (IOSE-29)(35). In hens study, flaxseed mediated reduction in the severity of ovarian cancer, correlated to the reduction in PGE2 in the ovaries of flaxseed-fed hens(36). The Southern Illinois University study also indicated the effective of long term flaxseed enriched diet in decreased ovarian cancer incidence and prostaglandin E₂in hens(37).

Taking altogether, without going into reviews, the list above have found effectively in reduced risk and treatment of ovarian cancer, but further studies with large example size and multi centers are necessary to identify the principle ingredients to validate the their effectiveness. As always, All articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.
Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve 
Optimal Health And Loose Weight

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 Most common Types of Cancer  http://kylejnorton.blogspot.ca/p/blog-page.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca  
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) Cruciferous vegetables consumption and the risk of ovarian cancer: a meta-analysis of observational studies by Han B, Li X, Yu T(PubMed)
(2) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM¹, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
(3) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation by Chen H¹, Landen CN, Li Y, Alvarez RD, Tollefsbol TO(PubMed)
(4) Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells by Bryant CS¹, Kumar S, Chamala S, Shah J, Pal J, Haider M, Seward S, Qazi AM, Morris R, Semaan A, Shammas MA, Steffes C, Potti RB, Prasad M, Weaver DW, Batchu RB(PubMed).
(5) 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)
(6) S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro by Xu YS¹, Feng JG², Zhang D³, Zhang B⁴, Luo M³, Su D⁵, Lin NM(PubMed)
(7) A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression by Chu Q¹, Ling MT, Feng H, Cheung HW, Tsao SW, Wang X, Wong YC.(PubMed)
(8) Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe by Kim JS¹, Lee SI, Park HW, Yang JH, Shin TY, Kim YC, Baek NI, Kim SH, Choi SU, Kwon BM, Leem KH, Jung MY, Kim DK.(PubMed)
(9) Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe by Kim JS¹, Lee SI, Park HW, Yang JH, Shin TY, Kim YC, Baek NI, Kim SH, Choi SU, Kwon BM, Leem KH, Jung MY, Kim DK.(PubMed)
(10) Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK by Weir NM¹, Selvendiran K, Kutala VK, Tong L, Vishwanath S, Rajaram M, Tridandapani S, Anant S, Kuppusamy P.(PubMed)
(11) Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells by Tan X¹, Sidell N, Mancini A, Huang RP, Shenming Wang, Horowitz IR, Liotta DC, Taylor RN, Wieser F.(PubMed)
(12) Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling by Watson JL¹, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, Hoskin DW.(PubMed)
(13) Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women by Cramer DW¹, Kuper H, Harlow BL, Titus-Ernstoff L.(PubMed)
(14) Dietary risk factors for ovarian cancer: the Adventist Health Study (United States) by Kiani F¹, Knutsen S, Singh P, Ursin G, Fraser G.(PubMed)
(15) The U.S. Food and Drug Administration's evidence-based review for qualified health claims: tomatoes, lycopene, and cancer by Kavanaugh CJ¹, Trumbo PR, Ellwood KC(PubMed)
(16) Induced growth of BG-1 ovarian cancer cells by 17β-estradiol or various endocrine disrupting chemicals was reversed by resveratrol via downregulation of cell cycle progression by Kang NH¹, Hwang KA, Kim TH, Hyun SH, Jeung EB, Choi KC.(PubMed)
(17) Resveratrol exerts differential effects in vitro and in vivo against ovarian cancer cells by Stakleff KS¹, Sloan T, Blanco D, Marcanthony S, Booth TD, Bishayee A.(PubMed)
(18) Resveratrol-induced autophagocytosis in ovarian cancer cells by Opipari AW Jr¹, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR.(PubMed)
(19) Oncogenic MicroRNA-27a is a target for genistein in ovarian cancer cells by Xu L¹, Xiang J, Shen J, Zou X, Zhai S, Yin Y, Li P, Wang X, Sun Q.(PubMed)
(20) Genistein, a soy phytoestrogen, prevents the growth of BG-1 ovarian cancer cells induced by 17β-estradiol or bisphenol A via the inhibition of cell cycle progression by Hwang KA¹, Kang NH, Yi BR, Lee HR, Park MA, Choi KC.(PubMed)
(21) Apoptosis induced by 7-difluoromethoxyl-5,4'-di-n-octyl genistein via the inactivation of FoxM1 in ovarian cancer cells by Ning Y¹, Li Q, Xiang H, Liu F, Cao J.(PubMed)
(22) Mediterranean diet, olive oil and cancer by Colomer R¹, Menéndez JA.(PubMed)
(23) Olive oil, seed oils and other added fats in relation to ovarian cancer (Italy) by Bosetti C¹, Negri E, Franceschi S, Talamini R, Montella M, Conti E, Lagiou P, Parazzini F, La Vecchia C.(PubMed)
(24) Mediterranean dietary traditions for the molecular treatment of human cancer: anti-oncogenic actions of the main olive oil's monounsaturated fatty acid oleic acid (18:1n-9) by Menendez JA¹, Lupu R.(PubMed).
(25) Green tea consumption enhances survival of epithelial ovarian cancer by Zhang M¹, Lee AH, Binns CW, Xie X.(PubMed)
(26) Possible role for green tea in ovarian cancer prevention by Lee AH¹, Fraser ML, Binns CW.(PubMed)
(27) Epigallocatechin‑3‑gallate inhibits the proliferation and migration of human ovarian carcinoma cells by modulating p38 kinase and matrix metalloproteinase‑2 by Wang F, Chang Z, Fan Q, Wang L.(PubMed)
(28) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation by Chen H¹, Landen CN, Li Y, Alvarez RD, Tollefsbol TO.(PubMed)
(29) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation by Chen H¹, Landen CN, Li Y, Alvarez RD, Tollefsbol TO.(PubMed)
(30) Antioxidant and cytotoxicity effect of rice bran phytic acid as an anticancer agent on ovarian, breast and liver cancer cell lines by Norhaizan ME¹, Ng SK, Norashareena MS, Abdah MA.(PubMed)
(31) The antioxidant and antiproliferative activities of methanolic extracts from Njavara rice bran by Rao AS¹, Reddy SG, Babu PP, Reddy AR.(PubMed)
(32) Intake of omega-3 and omega-6 fatty acids and risk of ovarian cancer by Ibiebele TI¹, Nagle CM, Bain CJ, Webb PM.(PubMed)
 (33) Meat, fish, and ovarian cancer risk: Results from 2 Australian case-control studies, a systematic review, and meta-analysis by Kolahdooz F¹, van der Pols JC, Bain CJ, Marks GC, Hughes MC, Whiteman DC, Webb PM; Australian Cancer Study (Ovarian Cancer) and the Australian Ovarian Cancer Study Group.(PubMed)
(34) Anti-inflammatory effects of fish oil in ovaries of laying hens target prostaglandin pathways by Eilati E, Small CC, McGee SR, Kurrey NK, Hales DB¹(PubMed)

(35) The effects of Omega-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines by Sharma A¹, Belna J, Logan J, Espat J, Hurteau JA(PubMed)
(36) Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E(2) in laying hen ovaries by Eilati E¹, Hales K, Zhuge Y, Ansenberger Fricano K, Yu R, van Breemen RB, Hales DB(PubMed)
(37) Long term consumption of flaxseed enriched diet decreased ovarian cancer incidence and prostaglandin E₂in hens by Eilati E¹, Bahr JM, Hales DB.(PubMed)

Alzheimer's disease in B Vitamins Points of view

Kyle J. Norton (Draft article)

Alzheimer's disease is a brain disorder correlated with major reductions in the addition of new neurons to the respective target areas through destruction of brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal. According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease.
The B Vitamin are a group of water-soluble vitamins found abundantly in whole grains, potatoes, bananas, lentils, chili peppers, tempeh, beans, nutritional yeast, brewer's yeast,  molasses, etc. The vitamin is essential for normal cellular growth and function and best known for converting energy from protein, fat, and carbohydrates during metabolism.

1. B vitamins and elevated plasma homocysteine
Hyperhomocysteinemia is one of the risk factors inducing the onset of AD.(1). B vitamins showed to slow the atrophy of specific brain regions which contribute to cognitive decline and influenced the progression of Alzheimer's' disease, through lowering elevated plasma homocysteine, according to the University of Oxford(2). A ingle-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment confirmed the homocysteine-lowering by B vitamins through inhibition of accelerated brain atrophy in prevention of mild cognitive impairment conversion to Alzheimer's disease.(3)(4). Raising plasma total homocysteine may be a strong prognostic marker of future cognitive decline, by targeting the low-normal concentrations of the B vitamins in lowering the levels of elevated of homocysteine concentrations, but large-scale randomized trials of homocysteine-lowering vitamins are necessary to validate these effectiveness(5).

2. The conflict results
Epidemiological studies, linking dietary supplementation of B vitamin in reduced risk of Alzheimers' diseases have been inclusive. According to the study at the School of Medicine, Qingdao University, dietary supplementation of antioxidants, including B vitamins, are beneficial to AD(6). Other study suggest that a formula of shilajit with B complex vitamins, may emerge as novel nutraceutical with potential uses against this brain disorder(7). Some researchers suggested that nutritional compositions, including B vitamins to stimulate synapse formation (between neurons in the nervous system) effectively reduce Alzheimer Disease neuropathology. These preclinical models provides a solid basis to predict potential to modify the disease process, especially during the early phases of Alzheimer Disease(8).
 On the other hand, the study by University of California in a multicenter, randomized, double-blind controlled clinical trial, indicated that high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD and In 89 patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) randomized study, no statistically significant beneficial effects on cognition or change in performance of activities of daily living (ADLs) function between multivitamin and placebo at 26 weeks(8).

Taking altogether, B vitamins may be effective in reduced levels of Hyperhomocysteinemia of which indicated an early onset of Alzheimers' disease. Combination use of B vitamins and other micronutrients and antioxidants may be associated in reduced risk and treatment of the disease. 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) [The clinical studies of hyperhomocysteinemia and Alzheimer's disease].[Article in Chinese]by Li YL¹, Hou Y, Niu C, Yu LX, Cheng YY, Hong Y.(PubMed)

(2) Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment by Douaud G¹, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD(PubMed)
(3) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial by Smith AD¹, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H(PubMed)
(4) Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment by Douaud G¹, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD.(PubMed)
(5) The worldwide challenge of the dementias: a role for B vitamins and homocysteine? by Smith AD.(PubMed)
(6) Nutrition and the risk of Alzheimer's disease by Hu N¹, Yu JT, Tan L, Wang YL, Sun L, Tan L.(PubMed)
(7) Can nutraceuticals prevent Alzheimer's disease? Potential therapeutic role of a formulation containing shilajit and complex B vitamins by Carrasco-Gallardo C¹, Farías GA, Fuentes P, Crespo F, Maccioni RB.(PubMed)
(8) The potential role of nutritional components in the management of Alzheimer's Disease by van der Beek EM¹, Kamphuis PJ.(PubMed)
(9) High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial by Aisen PS¹, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ; Alzheimer Disease Cooperative Study(PubMed)
(10) Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients by Sun Y¹, Lu CJ, Chien KL, Chen ST, Chen RC.(PubMed)

Alzheimer's disease in Vitamin E Points of view

Alzheimer's disease is a brain disorder correlated with major reductions in the addition of new neurons to the respective target areas through destruction of brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal.
According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease.
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..

1. The serum of vitamin E
Epidemiological studies, in determination of the form of vitamin E in reduced risk of Alzheimers disease have been inclusive. According to the joint study by the University and University of Perugia,  elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults(1). In other study of vitamin E and risk if AD in advanced age, high plasma levels of beta-tocopherol was associated to reduced risk of developing AD but levels of alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model(2).In the differentiation of vitamin E marker in mild cognitive impairment (MCI) from cognitively intact control (CTL) subjects, suggested that nutritional biomarkers detected in plasma-tocopherols and tocotrienols-as indirect indicators of the onset of AD(3). Other researchers suggest that various tocopherol forms rather than alpha- tocopherol alone may be important in the vitamin E protective association with Alzheimer disease(4) and low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD(5)(6).

2. The conflict results
A Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD, combination of 2000 IU/d of alpha tocopherol and memantine, exhibited the slower functional decline in mild to moderate AD(7). A placebo-controlled, clinical trial of vitamin E in patients with moderately advanced Alzheimer disease treatment with with 2000 IU (1342 alpha-tocopherol equivalents) vitamin E/d. may slow functional deterioration and prevent a clinical diagnosis of Alzheimer disease in elderly persons with mild cognitive impairment(8).  In the testing of the hypothesis of oxygen free radicals are probably involved in the deterioration of cognitive function, showed a positive effect of  alpha-tocopherol in reduced risk of the cognitive impairment but in consistent for women taking vitamin E alone, with no evidence of higher scores with longer durations of use(9). The double-blind, randomised trials in which treatment with vitamin E at any dose was compared with placebo for patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) showed a positive effects of the vitamin E in  treatment of AD or MCI, but future trials assessing vitamin E treatment in AD should not be restricted to alpha-tocopherol(10). Unfortunately, there is no evidence of vitamin E in in the prevention or treatment of people with AD or MCI, according to the study by the Milton Court Resourse Centre(11) and The Maudsley Hospital(12).

Taking altogether, without going into reviews, serum of vitamin E may be used as an indicator for the early onset and in reduced risk and treatment of Alzheimers' disease. 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.

References
(1) Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults by Mangialasche F¹, Solomon A, Kåreholt I, Hooshmand B, Cecchetti R, Fratiglioni L, Soininen H, Laatikainen T, Mecocci P, Kivipelto M.(PubMed)
(2) High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age by Mangialasche F¹, Kivipelto M, Mecocci P, Rizzuto D, Palmer K, Winblad B, Fratiglioni L.(PubMed)
(3) Classification and prediction of clinical diagnosis of Alzheimer's disease based on MRI and plasma measures of α-/γ-tocotrienols and γ-tocopherol by Mangialasche F¹, Westman E, Kivipelto M, Muehlboeck JS, Cecchetti R, Baglioni M, Tarducci R, Gobbi G, Floridi P, Soininen H, Kłoszewska I, Tsolaki M, Vellas B, Spenger C, Lovestone S, Wahlund LO, Simmons A, Mecocci P; AddNeuroMed consortium.(PubMed)
(4) Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change by Morris MC¹, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, Scherr PA(PubMed)

(5) Tocopherols and tocotrienols plasma levels are associated with cognitive impairment by Mangialasche F¹, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, Cecchetti R, Baglioni M, Simmons A, Soininen H, Tsolaki M, Kloszewska I, Vellas B, Lovestone S, Mecocci P; AddNeuroMed Consortium.(PubMed)
(6) Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults by Mangialasche F¹, Solomon A, Kåreholt I, Hooshmand B, Cecchetti R, Fratiglioni L, Soininen H, Laatikainen T, Mecocci P, Kivipelto M.(PubMed)

(7) Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial by Dysken MW¹, Sano M², Asthana S³, Vertrees JE⁴, Pallaki M⁵, Llorente M⁶, Love S¹, Schellenberg GD⁷, McCarten JR¹, Malphurs J⁸, Prieto S⁸, Chen P⁵, Loreck DJ⁹, Trapp G¹⁰, Bakshi RS¹⁰, Mintzer JE¹¹, Heidebrink JL¹², Vidal-Cardona A¹³, Arroyo LM¹³, Cruz AR¹⁴, Zachariah S¹⁴, Kowall NW¹⁵, Chopra MP¹⁵, Craft S¹⁶, Thielke S¹⁶, Turvey CL¹⁷, Woodman C¹⁷, Monnell KA¹⁸, Gordon K¹⁸, Tomaska J¹, Segal Y¹, Peduzzi PN¹⁹, Guarino PD.(PubMed)
(8) Vitamin E and Alzheimer disease: the basis for additional clinical trials by Grundman M.(PubMed)
(9) High-dose antioxidant supplements and cognitive function in community-dwelling elderly women by Grodstein F¹, Chen J, Willett WC.(PubMed)
(10) Vitamin E for Alzheimer's dementia and mild cognitive impairment by Farina N¹, Isaac MG, Clark AR, Rusted J, Tabet N.(PubMed|)
(11) Vitamin E for Alzheimer's disease and mild cognitive impairment by Isaac MG¹, Quinn R, Tabet N.(PubMed)
(12) Vitamin E for Alzheimer's disease by Tabet N¹, Birks J, Grimley Evans J.(PubMed)