Thursday, February 27, 2014

Vitamin A and Endometrial Cancer

 Kyle J. Norton

The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as  BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain Vitamins, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.

Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
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 of endometrial cancer have been inclusive.
1. Retinols
 The Istituto di Ricerche Farmacologiche Mario Negr study in dietary intake of carotenoids and retinol showed no association of retinols in reduced risk of endometrial cancer(5). In the Ishikawa endometrial cancer cell line, Retinoic acid is a metabolite of Retinol inhibited cell proliferation and the expression of RAR(retinoic acid receptor) alpha, RAR beta, and RAR gamma in the Ishikawa endometrial cancer cell line(6). the University Feinberg School of Medicine study in assessing the roles of RA and the RA agonist (AM580) in the growth of endometrial cancer cells, found that both RA and AM580 markedly inhibited endometrial cancer cell proliferation(7). Fenofibrate, an agonist of PPAR-alpha, potentiated by retinoic acid inhibited G1/S phase progression of endometrial cells through the cell cycle arrest(8). In endometrial carcinoma cells line (RL 95-2), RAs exerted its inhibitory effect on the growth of RL 95-2 cells through the estrogen pathway in estrogen-responsive endometrial cancer cells(9) or by interfering with the epidermal growth factor receptor (EGF-R) signaling pathway(10).

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. The Brigham and Women's Hospital and Harvard Medical School, in the study of antioxidants intake and risk of endometrial cancer, found no association between intakes of vitamins A, C, E or carotenoids from foods or supplements and cancer risk(11). In a dose-response meta-analysis, intakes of beta-carotene is associated to an inverse risk of endometrial cancer(12). the Medical University of Białystok study in the study suggested that endometrioid adenocarcinoma may be associated to certain enzymatic defects in carotenoid metabolism in the course of the neoplastic process or some metabolic modifications(13). The population-based case-control study in Shanghai, China of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls, indicated that dietary macronutrients with endometrial cancer associated to cancer risk may depend on the sources, dietary retinol, beta-carotene may decrease the risk of endometrial cancer(14)(15)

Taking altogether, without going into reviews, vitamin A may be associated to reduced risk and treatment of endometrial cancer through inhibition of cell cycle progression, modification of cells differentiated mechanisms. Overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)
(5) Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study by Pelucchi C1, Dal Maso L, Montella M, Parpinel M, Negri E, Talamini R, Giudice A, Franceschi S, La Vecchia C.(PubMed)
(6) Expression of retinoic acid receptors in human endometrial carcinoma by Tanabe K1, Utsunomiya H, Tamura M, Niikura H, Takano T, Yoshinaga K, Nagase S, Suzuki T, Ito K, Matsumoto M, Hayashi S, Yaegashi N(PubMed)
(7) Retinoic acid inhibits endometrial cancer cell growth via multiple genomic mechanisms by Cheng YH1, Utsunomiya H, Pavone ME, Yin P, Bulun SE(PubMed)
(8) In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer by Saidi SA1, Holland CM, Charnock-Jones DS, Smith SK(PubMed)
(9) Divergent effects of retinoic acids on the expression of ERalpha and 17beta-hydroxysteroid dehydrogenase type 2 in endometrial carcinoma cells (RL 95-2) by Li XH1, Li H, Xiao ZJ, Piao YS.(PubMed)
(10) Retinoic acid affects the EGF-R signaling pathway during differentiation induction of human endometrial adenocarcinoma cells by Carter CA1, Shaw BL(PubMed)
(11) Antioxidant intake and risk of endometrial cancer: results from the Nurses' Health Study by Cui X1, Rosner B, Willett WC, Hankinson SE(PubMed)
(12) Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis by Bandera EV1, Gifkins DM, Moore DF, McCullough ML, Kushi LH.(PubMed)
(13) Dietary carotenoids in normal and pathological tissues of corpus uteri by Czeczuga-Semeniuk E1, Wołczyński S(PubMed)
(14) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH1, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(15) Intake of selected micronutrients and the risk of endometrial carcinoma by Negri E1, La Vecchia C, Franceschi S, Levi F, Parazzini F.(PubMed)










Wednesday, February 26, 2014

Endometrial Cancer In Herbs' Points of View

 Kyle J. Norton(Draft Article)

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

1. 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. In mice study, licorice showed to inhibited the proliferation of endometrial carcinogenesis, through a significant decrease in the COX-2, IL-1alpha and TNF-alpha mRNA expressions(5). On estrogen-related endometrial carcinogenesis in mice, treatment after 2 weeks, licorice inhibited the E2-related endometrial carcinogenesis, through suppression of estrogen-induced c-fos/jun(a variety of physiological functions including cell proliferation and differentiation)-expressions(6).

2. 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 years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Catechins. the major polyphenols in green tea, showed to reduced risk reduction of  endometrial cancer(7). Epigallocatechin-3-gallate, Another biological active component of green tea, also
inhibited endometrial cancer cell line (Ishikawa cells) proliferation, through cell cycle arrest, interfered with Akt(role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration.) activation and MAPK(role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis) signals, and increased apoptosis signals leading to a controlled caspases(mechanisms of apoptosis), Bcl-2(family of regulator proteins that regulate cell death), Bax(involved in p53-mediated apoptosis) genes and protein expression.(8). In a study of 152 patients with histopathologically diagnosed EEA(endometrial cancer), and 285 healthy women of the control who were matched for age and area of residence with individual cases, showed that green tea have an inverse association to endometrial cancer risk regardless of the presence or absence of factors such as obesity and menopause(9).
 
3. Turmeric
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 traditional 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 constituent of turmeric, inhibited endometrial cancer proliferation through suppresses JAK-STAT(mechanisms of activation and regulation of this essential signaling cascade) signaling via activation of PIAS-3(Protein inhibitor of activated STAT3), thus attenuating STAT-3(signal transducer and activator of transcription-3 (STAT-3) is constitutively activated in ovarian and endometrial cancers) phosphorylation and tumor cell growth(10). In comparison of the effects of letrozole and curcumin in endometrial cancer in nude mice, treatment of curcumin or letrozole induced apoptosis in endometrial cancer and the composition further enhanced the inhibitory rate in tumor growth(11). In human endometrial carcinoma HEC-1-A cells, curcumin induced apoptosis through down-regulation of Ets-1 and Bcl-2 expression(12)

4. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
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(13). Purified allicin, a major ingredient of crushed garlic, showed to induced apoptosis through induction of activation of caspases-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase(14) A multi-centre case-control study of 454 endometrial cancer cases and 908 controls, allium vegetables, including garlic showed a moderate protective effect in reduced risk endometrial cancer(15). But according to the Korea Food and Drug Administration, there was no credible evidence to support a  garlic intake in reduced risk of endometrial cancer(16).

5. 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.
A recent report identified a variety of terpenoids inhibited cancer cell proliferation and metastasis via various mechanisms(17), including inhibition of tumor-induced angiogenesis and of various oncogenic and anti-apoptotic signaling pathways and suppression or nuclear translocation of various transcription factors including nuclear factor kappa B (NF-κB)(18).Terpenoids, a chemical constituent found in the Steam Distilled Extract of Ginger (SDGE) induced apoptosis through activating p53(tumor antigen)(19).

6. 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). In the study of the effect of several fractions of 6-yr old fresh ginseng and red ginseng, four semi-synthetic ginsenoside Rh1, Rh2, Rg3 and Rg5, major saponin components in red ginseng,suggested that ginsenoside Rg3, Rg5 and Rh2 shwed anticarcinogensis actively. Rg3, Rg5 and Rh2 are active components in red ginseng prevent cancer either singularly or synergistically(20). Ginsenoside-Rb2 derived from ginseng inhibited proliferation of endometrial cancer cell lines  Ishikawa(21). In precancerous lesions of the esophagus and endometrium, Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs(22).

7. Red clover
Red Clover is a short-lived perennial plant, in the genus Trifolium, belonging to the family Fabaceae, native to to Europe, Western Asia and northwest Africa. The herb has been used in traditional medicine as diuretic and liver cleansing agent and to treat cancer, whooping cough, respiratory problems, and skin inflammations, etc.
Synthesized carbamate esters with long aliphatic chains without such atoms from Biochanin A (BCA), a major isoflavone in red clover, suppressed cell proliferation Ishikawa cell line(22). the University of Illinois at Chicago study indicated that the flower head and total above-ground parts extracts exhibited differential estrogenic activity in an Ishikawa (endometrial) cel line and autohydrolytic extracts of above-ground parts contained more isoflavones and had more estrogenic activity in Ishikawa endometrial cells as compared with extracts of flower heads(23) and red clover isoflavones had an antiproliferative effect in the endometrium(24).

7. Scutellaria baicalensis (Baikal Skullcap, Huang Qin)
Baikal Skullcap, also known as Huang Qin in traditional Chinese medicine, is a flower plant of the genus Scutellaria belonging to the family Lamiaceae, native to China. The herb has been used to treat jaundice,  hypertension ,
anxiety, headache due to cold or flu, prostate Cancer, breast cancer,  red eyes and sore throat, cough
and asthma.
In endometrial cancer cell lines, high does of Huang Qin significantly inhibition of cell growth but
while lower doses stimulated growth in endometrial cell lines(25). In an estrogen-responsive mouse
tumor cell line, the herb Scutellaria baicalensis, significantly inhibited the proliferation of B-1F
cells(estrogen-responsive mouse tumor cell line B-1F ) in vitro and in vivo, through induction of DNA
fragmentation and morphological changes(26).

8. Fritillaria cirrhose (Chuan Bei Mu)
Fritillaria cirrhose is a bulbous plants in the genus of Fritillaria belonging to the family Liliaceae, native to the Northern Hemisphere. The herb has been used in traditional Chinese medicine  as as antibiotic and to raise blood pressure, stop cough, , increased blood sugar,etc. as it transforms Phlegm, calms cough; clears Heat, dissolves nodules, etc. by enhancing the functions of heart and lung channels.
In the composition study of Scutellaria baicalensis (SB) and Fritillaria cirrhosa (FC), suggested that both herb inhibit the proliferation of endometrial cell line through activation of caspase-3(cell apoptosis) G0 /G1 phase cell cycle arrest, down regulation of cyclins D1 and D3(regulating cell cycle progression) and induction of p27(Cell cycle inhibition)(27)

9. Bufalin (Chan Su)
Bufalin is also known as toad venom. The acrid, warm, toxic herb has been used in TCM to food poisoning with stomach pain and bloating, vomiting, diarrhea, fainting, painful and swollen throat and certain types of cancer, including liver cancer, intestine cancer, leukemia, skin cancer etc. as it expels toxins, resolves oedema, calms pain, opens the orifices, etc. by enhancing the functions of heart, kidney and stomach channels. Bufalin, the cardioactive C-24 steroids was found to inhibit the growth of tumors of endometrium through cell cycle arrest, apoptosis, and expression of genes proliferation genes(28). The Oita University Faculty of Medicine study also showed that Cang Su indiced apoptosis through decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases of the cell cycle(29).

11. The compositions Shi-Quan-Da-Bu-Tang or Shimotsu-to
Shi-Quan-Da-Bu-Tang is a composition of RenShen, BaiZhu, FuLing, ShuDiHuang, DangQui, Chuan Xiong, HuanQi and RuGui commonly used in traditional Chinese medicine to treat qi and blood accompanied by yang deficiency and cold manifestations. In endometrial cell line, the composition induced apoptosis of the cancer cells through suppression of the suppression of The expression of ER-alpha mRNA, but not ER-beta mRNA(30). Juzen-taiho-to, consisting a mixture of Shimotsu-to and Shikunshi-to formulas, in mice study showed to exert protective effect against estrogen-related endometrial carcinogenesis(31) through suppression of estradiol-17 beta (E2)-induced expression of c-fos/jun(cell proliferation, differentiation and survival) in uterine corpus and inhibition of N-methyl-N-nitrosourea(a highly reliable carcinogen, mutagen, and teratogen) and E2-induced endometrial carcinogenesis(32).

 Taking altogether, without going into reviews, the above list are found ti be effective in reduced risk and treatnent of endometrial cancer through various expressions and mechanisms including cell cycle arrest, upregulation of induced apopticand  downregulation of proliferative expressions. Large sample size and muticenter studies are necessary with identification of the active principle in order to improve the validation of the clinical trial.


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

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to Obesity  http://kylejnorton.blogspot.ca/p/obesitys-complications.html

References
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)
(5) Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice by Niwa K1, Lian Z, Onogi K, Yun W, Tang L, Mori H, Tamaya T(PubMed)
(6) Preventive effects of Glycyrrhizae radix extract on estrogen-related endometrial carcinogenesis in mice by Niwa K1, Hashimoto M, Morishita S, Yokoyama Y, Mori H, Tamaya T(PubMed)
(7) Green tea and green tea catechin extracts: an overview of the clinical evidence by Johnson R1, Bryant S, Huntley AL.(PubMed)
(8) Antiproliferative and apoptotic effect of epigallocatechin-3-gallate on Ishikawa cells is accompanied by sex steroid receptor downregulation by Park SB1, Bae JW, Kim JM, Lee SG, Han M(PubMed)
(9) Case-control study of green tea consumption and the risk of endometrial endometrioid adenocarcinoma by Kakuta Y1, Nakaya N, Nagase S, Fujita M, Koizumi T, Okamura C, Niikura H, Ohmori K, Kuriyama S, Tase T, Ito K, Minami Y, Yaegashi N, Tsuji I(PubMed)
(10) Curcumin suppresses constitutive activation of STAT-3 by up-regulating protein inhibitor of activated STAT-3 (PIAS-3) in ovarian and endometrial cancer cells by Saydmohammed M1, Joseph D, Syed V(PubMed)
(11) [Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice].[Article in Chinese] by Liang YJ1, Zhang HM, Wu YZ, Hao Q, Wang JD, Hu YL(PubMed)
(12) Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells by Yu Z1, Shah DM(PubMed)
(13) 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)
(14) Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells by Oommen S, Anto RJ, Srinivas G, Karunagaran D.(PubMed)
(15) Allium vegetables intake and endometrial cancer risk by Galeone C, Pelucchi C, Dal Maso L, Negri E, Montella M, Zucchetto A, Talamini R, La Vecchia C.(PubMed)
(16) Garlic intake and cancer risk: an analysis using the Food and Drug Administration's evidence-based review system for the scientific evaluation of health claims by Kim JY, Kwon O(PubMed)
(17) Terpenoids: natural products for cancer therapy by Huang M1, Lu JJ, Huang MQ, Bao JL, Chen XP, Wang YT.(PubMed)
(18) Inhibition of tumor progression by naturally occurring terpenoids by Kuttan G1, Pratheeshkumar P, Manu KA, Kuttan R.(PubMed)
(18) Terpenoids from Zingiber officinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53 by Liu Y1, Whelan RJ, Pattnaik BR, Ludwig K, Subudhi E, Rowland H, Claussen N, Zucker N, Uppal S, Kushner DM, Felder M, Patankar MS, Kapur A.(PubMed)
(19) Terpenoids from Zingiber officinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53 ,by Liu Y1, Whelan RJ, Pattnaik BR, Ludwig K, Subudhi E, Rowland H, Claussen N, Zucker N, Uppal S, Kushner DM, Felder M, Patankar MS, Kapur A(PubMed)
(20) Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds by Yun TK1, Lee YS, Lee YH, Kim SI, Yun HY(PubMed)
(21) Inhibitory effect of ginsenoside-Rb2 on invasiveness of uterine endometrial cancer cells to the basement membrane by Fujimoto J1, Sakaguchi H, Aoki I, Toyoki H, Khatun S, Tamaya T.(PubMed)
(22) Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium by Bespalov VG1, Alexandrov VA, Limarenko AY, Voytenkov BO, Okulov VB, Kabulov MK, Peresunko AP, Slepyan LI, Davydov VV.(PubMed)
(22) Ester and carbamate ester derivatives of Biochanin A: synthesis and in vitro evaluation of estrogenic and antiproliferative activities by Fokialakis N1, Alexi X, Aligiannis N, Siriani D, Meligova AK, Pratsinis H, Mitakou S, Alexis MN.(PubMed)
(23) Seasonal variation of red clover (Trifolium pratense L., Fabaceae) isoflavones and estrogenic activity by Booth NL1, Overk CR, Yao P, Totura S, Deng Y, Hedayat AS, Bolton JL, Pauli GF, Farnsworth NR.(PubMed)
(24) A double-blind randomized study on the effects of red clover isoflavones on the endometrium by Hale GE1, Hughes CL, Robboy SJ, Agarwal SK, Bievre M(PubMed)
(25) The Chinese herbs Scutellaria baicalensis and Fritillaria cirrhosa target NFκB to inhibit proliferation of ovarian and endometrial cancer cells by Kavandi L1, Lee LR, Bokhari AA, Pirog JE, Jiang Y, Ahmad KA, Syed V.(PubMed)
(26) Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line by Murashima T1, Katayama H, Shojiro K, Nishizawa Y(PubMed)
(27) The Chinese herbs Scutellaria baicalensis and Fritillaria cirrhosa target NFκB to inhibit proliferation of ovarian and endometrial cancer cells by Kavandi L1, Lee LR, Bokhari AA, Pirog JE, Jiang Y, Ahmad KA, Syed V.(PubMed)
(28) Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells by Takai N1, Kira N, Ishii T, Yoshida T, Nishida M, Nishida Y, Nasu K, Narahara H.(PubMed)
(29) Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells by Takai N1, Ueda T, Nishida M, Nasu K, Narahara H.(PubMed)
(30)Anti-tumor effects of herbal medicines on endometrial carcinomas via estrogen receptor-alpha-related mechanism by Lian Z1, Niwa K, Onogi K, Mori H, Harrigan RC, Tamaya T(PubMed)
(31) Preventive effect of Juzen-taiho-to on endometrial carcinogenesis in mice is based on Shimotsu-to constituent by Tagami K1, Niwa K, Lian Z, Gao J, Mori H, Tamaya T.(PubMed)

(32) Cell proliferation in cancer prevention; effects of preventive agents on estrogen-related endometrial carcinogenesis model and on an in vitro model in human colorectal cells by Mori H1, Niwa K, Zheng Q, Yamada Y, Sakata K, Yoshimi N.(PubMed)
(33) Apoptotic effects of Tian-Long compound on endometrial adenocarcinoma cells in vitro by Li ZL1, Morishima S, Tang JT, Otsuki Y.(PubMed)

Tuesday, February 25, 2014

Endometrial Cancer - the Genes Mutation

Kyle J. Norton(Draft Article)

The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as  BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

Endometrium is the inner lining of the mammalian uterus and very susceptible hormone change, particular to menstrual cycle. Endometrial cancer is a late adulthood cancer defined as a condition of which the cells of the endometrial lining of uterus have growth uncontrollable or become cancerous as a result of the alternation of cells DNA. It's the fourth most common cancer among women overall, after breast cancer, lung cancer, and bowel cancer.

The genes mutation
1. BRCA1 or the BRCA2 gene 
Women who carry the genes BRCA1 or the BRCA2, according to Familial Breast Cancer Research study are associated to risk of endometrial cancer, specialty for  the gene BRCA, but the excessive risk is largely attributable to a history of Tamoxifen use.(1) and in aged group between 45 to 70(2).

2. Mutations in DNA mismatch repair (MMR) genes
Mutations in DNA mismatch repair (MMR) genes affects the DNA repair prowess, elevating endometrial cancer risk, due to the loss of proofreading activity of Polε (3). The University of Oxford, study, indicated that mutation of germline exonuclease domain ((EDMs) of POLE and POLD1 are associated to predispose to endometrial cancer (EC) risk(4), Other study showed that defection in either DNA proofreading or MMR may relate to genomic instability and tumourigenesis(5).

3. Phosphatase and tensin homolog (PTEN)
Mation of Mutations of this gene are aassociated ti the development of many types of cancer, specially in altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors(6)

4. K-ras mutations
K-ras gene are protein product plays an essential function in normal tissue signaling. Mutation of KRAS gene is associated to  the development of many cancers. According to the study by Haukeland University Hospital, KRAS mutations over amplification and expression were presented in 14.7% of primary lesions with no increase in metastatic lesions but in 18% of metastatic lesions. and high KRAS mRNA levels sre associated with aggressive phenotype due to activation of ERK1/2 , (in regulating the malignant potential of cancer cells)(7).According to the study by Kanazawa University, 23% of patients with endometrial cancer carry  a mutation in exon 1 of KRAS(7) and 70% of Mutation in codon 12 of the K-ras gene in Serbian patients(8)

5.  β-catenin mutation
β-catenin plays an important role in dual function protein by regulating the coordination of cell–cell adhesion and gene transcription, Mutation and over expression are associated to increased risk of endometrial cancer(9). The Sapporo Medical University study insisted that alternation of the beta-catenin gene occurs in atypical hyperplasia or cancer, rather than in simple or complex hyperplasia without atypia(structural abnormality in a cell), during endometrial carcinogenesis(10).
In an immunohistochemically analyzed 80 endometrial samples (30 of normal endometrium, 20 of endometrial hyperplasia, and 30 of endometrial cancer), beta-catenin was observed in 30% of endometrial cancer samples(11).

6. Lynch syndrome
Lynch syndrome is an inherited condition with increased  risk of colon and other cancers, caused by a germ line mutation in a mismatch repair gene(12). The risk of Lynch syndrome among endometrial cancer patients is 4.6%(13). In a molecular screening for LS in patients with endometrial cancer  ≤ 70 years of age, the risk of  LS is 6% of cases(14), Inactivation of the mismatch repair genes MSH2 and MSH6 are associated to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome)(15).

Taking altogether, genetic mutation of certain genes are associated with increased risk of endometrial cancer. Fortunately, certain foods and herbs have found to be effective in suppressing the expression and blocking the preoperative mechanism and pathways. Please note that 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 incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study by Segev Y, Iqbal J, Lubinski J, Gronwald J, Lynch HT, Moller P, Ghadirian P, Rosen B, Tung N, Kim-Sing C, Foulkes WD, Neuhausen SL, Senter L, Singer CF, Karlan B, Ping S, Narod SA; Hereditary Breast Cancer Study Group.(PubMed)
(2) The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations. A prospective study by Beiner ME, Finch A, Rosen B, Lubinski J, Moller P, Ghadirian P, Lynch HT, Friedman E, Sun P, Narod SA; Hereditary Ovarian Cancer Clinical Study Group(PubMed)
(3) A common cancer-associated DNA polymerase {varepsilon} mutation causes an exceptionally strong mutator phenotype, indicating fidelity defects distinct from loss of proofreading by Kane DP, Shcherbakova PV(PubMed)
(4) [Identification and management of HNPCC syndrome (hereditary non polyposis colon cancer), hereditary predisposition to colorectal and endometrial adenocarcinomas].
[Article in French by Olschwang S, Bonaïti C, Feingold J, Frébourg T, Grandjouan S, Lasset C, Laurent-Puig P, Lecuru F, Millat B, Sobol H, Thomas G, Eisinger F.(PubMed)
(5) DNA polymerase ε and δ exonuclease domain mutations in endometrial cancer by Church DN, Briggs SE, Palles C, Domingo E, Kearsey SJ, Grimes JM, Gorman M, Martin L, Howarth KM, Hodgson SV; NSECG Collaborators, Kaur K, Taylor J, Tomlinson IP(PubMed)
(6) Genetics of Endometrial Cancers by Tsuyoshi Okuda,1,* Akihiko Sekizawa,1 Yuditiya Purwosunu,1, 2 Masaaki Nagatsuka,1 Miki Morioka,1 Masaki Hayashi,1 and Takashi Okai(PubMed)
(7) KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer by Birkeland E, Wik E, Mjøs S, Hoivik EA, Trovik J, Werner HM, Kusonmano K, Petersen K, Raeder MB, Holst F, Øyan AM, Kalland KH, Akslen LA, Simon R, Krakstad C, Salvesen HB.(PubMed)
(8) Genetic alterations in SMAD4 and K-ras in Serbian patients with endometrial carcinoma by Nikolic A, Ristanovic M, Perovic V, Trifunovic J, Perovic M, Radojkovic D.(PubMed)
(9) Frequent β-catenin gene mutations in atypical polypoid adenomyoma of the uterus by Takahashi H, Yoshida T, Matsumoto T, Kameda Y, Takano Y, Tazo Y, Inoue H, Saegusa M(PubMed)
(10) Mutation of beta-catenin gene in endometrial cancer but not in associated hyperplasia by Ashihara K, Saito T, Mizumoto H, Nishimura M, Tanaka R, Kudo R.(PubMed)
(11) Nuclear localization of beta-catenin in normal and carcinogenic endometrium by Nei H, Saito T, Yamasaki H, Mizumoto H, Ito E, Kudo R.(PubMed)
(12) Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome by Win AK, Lindor NM, Winship I, Tucker KM, Buchanan DD, Young JP, Rosty C, Leggett B, Giles GG, Goldblatt J, Macrae FA, Parry S, Kalady MF, Baron JA, Ahnen DJ, Marchand LL, Gallinger S, Haile RW, Newcomb PA, Hopper JL, Jenkins MA(PubMed)
(13) Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers by Egoavil C, Alenda C, Castillejo A, Paya A, Peiro G, Sánchez-Heras AB, Castillejo MI, Rojas E, Barberá VM, Cigüenza S, Lopez JA, Piñero O, Román MJ, Martínez-Escoriza JC, Guarinos C, Perez-Carbonell L, Aranda FI, Soto JL.(PubMed)
(14) Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years by Leenen CH, van Lier MG, van Doorn HC, van Leerdam ME, Kooi SG, de Waard J, Hoedemaeker RF, van den Ouweland AM, Hulspas SM, Dubbink HJ, Kuipers EJ, Wagner A, Dinjens WN, Steyerberg EW.(PubMed)
(15) Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities Michael A. Edelbrocka,, Saravanan Kaliyaperumalb, , Kandace J. Williams(Science direct)



Sunday, February 23, 2014

Prostate cancer in Vitamin B12's Points of View


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.

Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.


Epidemiological studies linking levels of plasma of vitamin B12 in reduced risk of prostate cancer have produced inconclusive results, it may be due to single nucleotide polymorphisms in B(12)-related genes (MTR, MTRR, FUT2, TCN2, TCN1, CUBN, and MUT), tTC(involved in many processes in the body, such as protein production, protein transport, and the cycle of cell division), holo-transcobalamin(markers of vitamin B12 deficiency), holo-haptocorrin, folate, and homocysteine(a non-protein α-amino acid and can be recycled into methionine or converted into cysteine with the aid of B-vitamins)(1). Study from the University of Bristol, showed the increased B12 and holo-haptocorrin concentrations associated to positive correlation with prostate cancer risk(2)(3). But the University of Bergen, in a prospective cohort in Norway (n = 317 000) study,  showed no association between vitamin B12 status and prostate cancer risk(4).
In a clinical trial of dietary supplements and prostate cancer, found that a combination of antioxidants, isoflavones, lycopenes, minerals, plant oestrogens and vitamins, including vitamin B12 significantly decreased PSA levels compared with placebo(5).

Taking altogether, without going into reviews, combination of treatment included vitamin B12 may be associated to reduced risk of prostate cancer. 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) The causal roles of vitamin B(12) and transcobalamin in prostate cancer: can Mendelian randomization analysis provide definitive answers by Collin SM, Metcalfe C, Palmer TM, Refsum H, Lewis SJ, Smith GD, Cox A, Davis M, Marsden G, Johnston C, Lane JA, Donovan JL, Neal DE, Hamdy FC, Smith AD, Martin RM.(PubMed)
(2) Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis by Collin SM, Metcalfe C, Refsum H, Lewis SJ, Zuccolo L, Smith GD, Chen L, Harris R, Davis M, Marsden G, Johnston C, Lane JA, Ebbing M, Bønaa KH, Nygård O, Ueland PM, Grau MV, Baron JA, Donovan JL, Neal DE, Hamdy FC, Smith AD, Martin RM(PubMed)
(3) Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study by Hultdin J, Van Guelpen B, Bergh A, Hallmans G, Stattin P.(PubMed)

(4) Serum folate and vitamin B12 concentrations in relation to prostate cancer risk--a Norwegian population-based nested case-control study of 3000 cases and 3000 controls within the JANUS cohort by de Vogel S, Meyer K, Fredriksen Å, Ulvik A, Ueland PM, Nygård O, Vollset SE, Tell GS, Tretli S, Bjørge T.(PubMed)
(5) Dietary supplements and prostate cancer: a systematic review of double-blind, placebo-controlled randomised clinical trials by Posadzki P, Lee MS, Onakpoya I, Lee HW, Ko BS, Ernst E.(PubMed)


Saturday, February 22, 2014

Vitamin D and Endometrial Cancer


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

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

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

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

Vitamin C and Endometrial Cancer

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

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

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




Prostate cancer in Vitamin K's Points of View

 Kyle J. Norton(Draft Article)

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

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

Taking altogether, co administration of synthetic vitamin K3 and other vitamins such as vitamin C is associated to reduced risk and treatment of prostate cancer, though cell cycle arrest, up regulation of 
anti profilerative and down regulation of cancer promoter pathways or inctreased oxidative stress. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.
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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
 

References
(1) In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K(3) combination by Taper HS, Jamison JM, Gilloteaux J, Gwin CA, Gordon T, Summers JL(PubMed)
(2) Scanning electron microscopy and transmission electron microscopy aspects of synergistic antitumor activity of vitamin C - vitamin K3 combinations against human prostatic carcinoma cells by Gilloteaux J, Jamison JM, Venugopal M, Giammar D, Summers JL(PubMed)
(3) Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway by Jiang Y, Yang J, Yang C, Meng F, Zhou Y, Yu B, Khan M, Yang H(PubMed)
(4) alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate by Tomasetti M, Strafella E, Staffolani S, Santarelli L, Neuzil J, Guerrieri R(PubMed)
(5) Cell death by autoschizis in TRAMP prostate carcinoma cells as a result of treatment by ascorbate: menadione combination by Gilloteaux J, Jamison JM, Neal DR, Summers JL(PubMed)
(6) Synergistic antitumour activity of vitamins C and K3 against human prostate carcinoma cell lines by Venugopal M, Jamison JM, Gilloteaux J, Koch JA, Summers M, Hoke J, Sowick C, Summers JL.(PubMed)
(7) Flow cytometric and ultrastructural aspects of the synergistic antitumor activity of vitamin C-vitamin K3 combinations against human prostatic carcinoma cells by Jamison JM, Gilloteaux J, Venugopal M, Koch JA, Sowick C, Shah R, Summers JL(PubMed)
(8) Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) by Nimptsch K, Rohrmann S, Kaaks R, Linseisen J.(PubMed)
(9) Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) by Nimptsch K, Rohrmann S, Linseisen J.(PubMed)








Thursday, February 20, 2014

Endometrial Cancer In Foods Points of View

Kyle J. Norton(Draft Article)

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

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

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

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

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

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

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

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

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

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

Taking altogether, without going into reviews, intake of above list foods are associated to reduced risk and treatment of endometrial cancer. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.
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