Journal of Literature Pharmacy Sciences

Fitoöstrojenler ve Meme Kanseri İlişkisi: Sistematik Derleme
Phytoestrogens and Breast Cancer Relationship: Systematic Review
Dilan AŞKIN ÖZEKa, Songül ÜNÜVARb
aFırat Üniversitesi Kovancılar Meslek Yüksekokulu, Eczane Hizmetleri Bölümü, Elazığ, TÜRKİYE
bİnönü Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Malatya, TÜRKİYE
J Lit Pharm Sci. 2021;10(3):322-31
doi: 10.5336/pharmsci.2021-83721
Article Language: TR
Full Text
ÖZET
Meme kanseri (MK), dünya çapında kadınlarda en sık görülen kanser türü olup, kansere bağlı ölümlerin 2. nedenidir. Yüksek düzeylerde östrojen ve türevlerine maruz kalmak, MK'nin gelişmesine neden olan ana etkenlerden biridir. MK tedavisinde kullanılan kemoterapi ilaçlarına bağlı gözlenen yan etkiler, ilaçlara karşı direnç gelişmesi ve hastalığın nüks etmesi gibi faktörler tedavi etkinliğini kısıtlamaktadır. Özellikle Evre 4, metastatik MK ile ilgili aydınlatılmamış pek çok nokta bulunmaktadır. Bu nedenle MK'nin önlenmesi ve tedavisiyle ilgili yeni yaklaşımların araştırılmasına ihtiyaç duyulmaktadır. Fitoöstrojenler, bitkilerden elde edilen ikincil metabolitler olarak kabul edilen polifenolik veya steroidal olmayan bileşiklerdir. Bu bileşikler, östrojen ve türevlerine yapısal ve işlevsel olarak benzemektedirler. Fitoöstrojenler, postmenapoz dönemde osteoporoz, sıcak basması ve terleme gibi şikâyetleri hafifletmek amacıyla kullanılmaktadırlar. Ancak fitoöstrojenlerin neden olduğu östrojen benzeri istenmeyen etkilerinden kaçınmak için fitoöstrojenlerin etkilerini ve doğru kullanımını anlamak oldukça önemlidir. Bu derlemede, MK ile en yaygın kullanılan fitoöstrojenler arasındaki ilişkinin kanserli hücre hatları, hayvan deneyleri ve insan çalışmalarıyla değerlendirildiği literatürlere yer verilmiştir.

Anahtar Kelimeler: Meme kanseri; fitoöstrojenler; östrojen; genistein; resveratrol
ABSTRACT
Breast cancer (BC) is the most common type of cancer in women worldwide and is the second cause of cancer-related deaths. Exposure to high levels of estrogen and its derivatives is one of the main factors leading to the development of BC. Factors such as side effects due to chemotherapy drugs used in the treatment of BC, development of resistance to drugs and relapse of the disease limit the effectiveness of the treatment. There are many unexplained points about metastatic BC, especially in the Stage 4. For this reason, there is a need to investigate new approaches regarding the prevention and treatment of BC. Phytoestrogens are polyphenolic or non-steroidal compounds that are considered secondary metabolites derived from plants. These compounds are structurally and functionally similar to estrogen and its derivatives. Phytoestrogens are used to alleviate complaints such as osteoporosis, hot flashes and sweating in the postmenopausal period. However, in order to avoid estrogen-like undesirable effects caused by of phytoestrogens, it is essential to understand the effects and correct use of phytoestrogens. This review includes literature evaluating the relationship between BC and the most commonly used phytoestrogens with cancer cell lines, animal experiments and human studies.

Keywords: Breast cancer; phytoestrogens; estrogen; genistein; resveratrol
REFERENCES:
  1. Rice-Evans C. Flavonoids and isoflavones: absorption, metabolism, and bioactivity. Free Radic Biol Med. 2004;36(7):827-8. [Crossref]  [PubMed] 
  2. De Flora S, Ferguson LR. Overview of mechanisms of cancer chemopreventive agents. Mutat Res. 2005;591(1-2):8-15. Epub 2005 Aug 16. [Crossref] [PubMed] 
  3. De Flora S, Izzotti A, D'Agostini F, Balansky RM, Noonan D, Albini A. Multiple points of intervention in the prevention of cancer and other mutation-related diseases. Mutat Res. 2001;480-1:9-22. [Crossref] [PubMed] 
  4. World Health Organization [İnternet]. © 2021 WHO. [Erişim tarihi: 26.03.2021]. Breast cancer. Erişim linki: [Link] 
  5. Jiang H, Fan J, Cheng L, Hu P, Liu R. The anticancer activity of genistein is increased in estrogen receptor beta 1-positive breast cancer cells. Onco Targets Ther. 2018;11:8153-63. [Crossref] [PubMed] [PMC] 
  6. Caferoğlu Z, Çiçek B. Fitoöstrojenler: yararlı mı, zararlı mı? [Phytoestrogens: Useful or Harmful ?]. Bes Diy Derg. 2014;42(3):234-41. [Link] 
  7. Özmen V. Breast cancer in Turkey: clinical and histopathological characteristics (analysis of 13.240 Patients). J Breast Health. 2014;10(2): 98-105. [Crossref] [PubMed] [PMC] 
  8. Levine JP. Treating menopausal symptoms with a tissue-selective estrogen complex. Gend Med. 2011;8(2):57-68. [Crossref] [PubMed] 
  9. Sinha D, Sarkar N, Biswas J, Bishayee A. Resveratrol for breast cancer prevention and therapy: preclinical evidence and molecular mechanisms. Semin Cancer Biol. 2016;40-1:209-32. [Crossref] [PubMed] 
  10. Jonsson P, Katchy A, Williams C. Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells. Endocr Relat Cancer. 2014;21(2):143-60. [Crossref] [PubMed] [PMC] 
  11. Chen LR, Chen KH. Utilization of isoflavones in soybeans for women with menopausal syndrome: an overview. Int J Mol Sci. 2021;22(6): 3212. [Crossref] [PubMed] [PMC] 
  12. Jiao J, Xiang H, Liao Q. Recent advancement in nonsteroidal aromatase inhibitors for treatment of estrogen-dependent breast cancer. Curr Med Chem. 2010;17(30):3476-87. [Crossref] [PubMed] 
  13. Cos P, De Bruyne T, Apers S, Vanden Berghe D, Pieters L, Vlietinck AJ. Phytoestrogens: recent developments. Planta Med. 2003;69(7): 589-99. [PubMed] 
  14. Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Grobbee DE, et al. Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2008;17(10):2632-8. [Crossref] [PubMed] 
  15. Matthews J, Celius T, Halgren R, Zacharewski T. Differential estrogen receptor binding of estrogenic substances: a species comparison. J Steroid Biochem Mol Biol. 2000;74(4):223-34. [Crossref] [PubMed] 
  16. Büyüktuncer Z, Başaran AA. Fitoöstrojenler ve sağlıklı yaşamdaki önemleri [Phytoestrogens and their importance in healthy life]. Hacettepe University Faculty of Pharmacy Journal. 2005;(2):79-94. [Link] 
  17. Basu P, Maier C. Phytoestrogens and breast cancer: In vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives. Biomed Pharmacother. 2018;107:1648-66. [Crossref] [PubMed] 
  18. Wang TT, Sathyamoorthy N, Phang JM. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis. 1996; 17(2):271-5. [Crossref] [PubMed] 
  19. Hwang CS, Kwak HS, Lim HJ, Lee SH, Kang YS, Choe TB, et al. Isoflavone metabolites and their in vitro dual functions: they can act as an estrogenic agonist or antagonist depending on the estrogen concentration. J Steroid Biochem Mol Biol. 2006;101(4-5):246-53. [Crossref] [PubMed] 
  20. Constantinou AI, White BE, Tonetti D, Yang Y, Liang W, Li W, et al. The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumours. Eur J Cancer. 2005;41(4):647-54. [Crossref] [PubMed] 
  21. Messina M, McCaskill-Stevens W, Lampe JW. Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. J Natl Cancer Inst. 2006; 98(18):1275-84. [Crossref] [PubMed] 
  22. Adlercreutz H, Mousavi Y, Clark J, Höckerstedt K, Hämäläinen E, Wähälä K, et al. Dietary phytoestrogens and cancer: in vitro and in vivo studies. J Steroid Biochem Mol Biol. 1992; 41(3-8):331-7. [Crossref] [PubMed] 
  23. Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21(2):113-31. [Crossref] [PubMed] 
  24. Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst. 2006;98(7):459-71. [PubMed] 
  25. Messina MJ, Loprinzi CL. Soy for breast cancer survivors: a critical review of the literature. J Nutr. 2001;131(11 Suppl):3095S-108S. [Crossref] [PubMed] 
  26. Chen HH, Chen SP, Zheng QL, Nie SP, Li WJ, Hu XJ, et al. Genistein promotes proliferation of human cervical cancer cells through estrogen receptor-mediated PI3K/Akt-NF-κB Pathway. J Cancer. 2018;9(2):288-95. [Crossref] [PubMed] [PMC] 
  27. Hsieh CY, Santell RC, Haslam SZ, Helferich WG. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1998;58(17):3833-8. Erratum in: Cancer Res. 1999;59(6):1388. [PubMed] 
  28. Hewitt AL, Singletary KW. Soy extract inhibits mammary adenocarcinoma growth in a syngeneic mouse model. Cancer Lett. 2003; 192(2):133-43. [Crossref] [PubMed] 
  29. Hilakivi-Clarke L, Onojafe I, Raygada M, Cho E, Skaar T, Russo I, et al. Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis. Br J Cancer. 1999; 80(11):1682-8. [Crossref] [PubMed] [PMC] 
  30. Pei RJ, Sato M, Yuri T, Danbara N, Nikaido Y, Tsubura A. Effect of prenatal and prepubertal genistein exposure on N-methyl-N-nitroso urea-induced mammary tumorigenesis in female Sprague-Dawley rats. In Vivo. 2003; 17(4):349-57. [PubMed] 
  31. Ju YH, Allred CD, Allred KF, Karko KL, Doerge DR, Helferich WG. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr. 2001;131(11):2957-62. [Crossref] [PubMed] 
  32. Allred CD, Allred KF, Ju YH, Clausen LM, Doerge DR, Schantz SL, et al. Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats. Carcinoge nesis. 2004;25(2):211-8. [Crossref] [PubMed] 
  33. Ju YH, Doerge DR, Woodling KA, Hartman JA, Kwak J, Helferich WG. Dietary genistein negates the inhibitory effect of letrozole on the growth of aromatase-expressing estrogen-dependent human breast cancer cells (MCF-7Ca) in vivo. Carcinogenesis. 2008;29(11): 2162-8. [Crossref] [PubMed] [PMC] 
  34. Ju YH, Doerge DR, Allred KF, Allred CD, Helferich WG. Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res. 2002;62(9):2474-7. [PubMed] 
  35. Chi F, Wu R, Zeng YC, Xing R, Liu Y, Xu ZG. Post-diagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies. Asian Pac J Cancer Prev. 2013; 14(4):2407-12. [Crossref] [PubMed] 
  36. Guha N, Kwan ML, Quesenberry CP Jr, Weltzien EK, Castillo AL, Caan BJ. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat. 2009;118(2):395-405. [Crossref] [PubMed] [PMC] 
  37. Shu XO, Zheng Y, Cai H, Gu K, Chen Z, Zheng W, et al. Soy food intake and breast cancer survival. JAMA. 2009;302(22):2437-43. [Crossref] [PubMed] [PMC] 
  38. Verheus M, van Gils CH, Keinan-Boker L, Grace PB, Bingham SA, Peeters PH. Plasma phytoestrogens and subsequent breast cancer risk. J Clin Oncol. 2007;25(6):648-55. [Crossref] [PubMed] 
  39. Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008;98(1):9-14. [Crossref] [PubMed] [PMC] 
  40. Maskarinec G, Takata Y, Franke AA, Williams AE, Murphy SP. A 2-year soy intervention in premenopausal women does not change mammographic densities. J Nutr. 2004; 134(11):3089-94. [Crossref] [PubMed] 
  41. Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, et al. Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res. 2004;6(3):R170-9. [Crossref] [PubMed] [PMC] 
  42. Petrakis NL, Barnes S, King EB, Lowenstein J, Wiencke J, Lee MM, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev. 1996;5(10):785-94. [PubMed] 
  43. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010;31(4):400-19. [Crossref] [PubMed] [PMC] 
  44. ?o?ić-Jurjević B, Filipović B, Sekulić M. Soybean phytoestrogens - friends or foes? Recent Trends for Enhancing the Diversity and Quality of Soybean Products. 2011;10:131-75. [Crossref] 
  45. Sirerol JA, Rodríguez ML, Mena S, Asensi MA, Estrela JM, Ortega AL. Role of natural stilbenes in the prevention of cancer. Oxid Med Cell Longev. 2016;2016:3128951. [Crossref] [PubMed] [PMC] 
  46. Stivala LA, Savio M, Carafoli F, Perucca P, Bianchi L, Maga G, et al. Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. J Biol Chem. 2001;276(25):22586-94. [Crossref] [PubMed] 
  47. Gehm BD, McAndrews JM, Chien PY, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S A. 1997;94(25):14138-43. [Crossref] [PubMed] [PMC] 
  48. Rimando AM, Suh N. Biological/chemopreventive activity of stilbenes and their effect on colon cancer. Planta Med. 2008;74(13):1635-43. [Crossref] [PubMed] 
  49. Horgan XJ, Tatum H, Brannan E, Paull DH, Rhodes LV. Resveratrol analogues surprisingly effective against triple negative breast cancer, independent of ERα. Oncol Rep. 2019;41(6):3517-26. [Crossref] [PubMed] 
  50. Pozo-Guisado E, Alvarez-Barrientos A, Mulero-Navarro S, Santiago-Josefat B, Fernandez-Salguero PM. The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle. Biochem Pharmacol. 2002;64(9):1375-86. [Crossref] [PubMed] 
  51. Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res. 2002;62(17): 4945- 54. [PubMed] 
  52. Garvin S, Ollinger K, Dabrosin C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett. 2006;231(1):113-22. [Crossref] [PubMed] 
  53. Provinciali M, Re F, Donnini A, Orlando F, Bartozzi B, Di Stasio G, et al. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2005;115(1):36-45. [Crossref]  [PubMed] 
  54. Bobrowska-Korczak B, Skrajnowska D, Tokarz A. The effect of dietary zinc--and polyphenols intake on DMBA-induced mammary tumorigenesis in rats. J Biomed Sci. 2012;19(1):43. [Crossref] [PubMed] [PMC] 
  55. Castillo-Pichardo L, Cubano LA, Dharmawardhane S. Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice. BMC Complement Altern Med. 2013;13:6. [Crossref] [PubMed] [PMC] 
  56. Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res. 2001; 61(20):7456-63. [PubMed] 
  57. Chow HH, Garland LL, Heckman-Stoddard BM, Hsu CH, Butler VD, Cordova CA, et al. A pilot clinical study of resveratrol in postmenopausal women with high body mass index: effects on systemic sex steroid hormones. J Transl Med. 2014;12:223. [Crossref] [PubMed] [PMC] 
  58. Zhu W, Qin W, Zhang K, Rottinghaus GE, Chen YC, Kliethermes B, et al. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr Cancer. 2012;64(3):393-400. [Crossref] [PubMed] [PMC] 
  59. Aehle E, Müller U, Eklund PC, Willför SM, Sippl W, Dräger B. Lignans as food constituents with estrogen and antiestrogen activity. Phytochemistry. 2011;72(18):2396-405. [Crossref] [PubMed] 
  60. Saleem M, Kim HJ, Ali MS, Lee YS. An update on bioactive plant lignans. Nat Prod Rep. 2005;22(6):696-716. [Crossref] [PubMed] 
  61. Xiong XY, Hu XJ, Li Y, Liu CM. Inhibitory effects of enterolactone on growth and metastasis in human breast cancer. Nutr Cancer. 2015;67(8):1324-32. [Crossref] [PubMed] 
  62. Feng XL, Ho SC, Zhan XX, Zuo LS, Mo XF, Zhang X, et al. Serum isoflavones and lignans and odds of breast cancer in pre- and postmenopausal Chinese women. Menopause. 2021;28(4):413-22. [Crossref] [PubMed] 
  63. McCann SE, Thompson LU, Nie J, Dorn J, Trevisan M, Shields PG, et al. Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat. 2010;122(1):229-35. [Crossref] [PubMed] [PMC] 
  64. Thanos J, Cotterchio M, Boucher BA, Kreiger N, Thompson LU. Adolescent dietary phytoestrogen intake and breast cancer risk (Ca nada). Cancer Causes Control. 2006;17(10): 1253-61. [Crossref] [PubMed] 
  65. Lowcock EC, Cotterchio M, Boucher BA. Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk. Cancer Causes Control. 2013;24(4):813-6. [Crossref] [PubMed] 
  66. Touillaud MS, Thiébaut AC, Fournier A, Niravong M, Boutron-Ruault MC, Clavel-Chapelon F. Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J Natl Cancer Inst. 2007;99(6):475-86. [Crossref] [PubMed] [PMC] 
  67. Zamora-Ros R, Ferrari P, González CA, Tjønneland A, Olsen A, Bredsdorff L, et al. Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. Breast Cancer Res Treat. 2013;139(1): 163-76. [Crossref] [PubMed] 
  68. Buck K, Zaineddin AK, Vrieling A, Heinz J, Linseisen J, Flesch-Janys D, et al. Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer. Br J Cancer. 2011;105(8):1151-7. [Crossref] [PubMed] [PMC] 
  69. Adams NR. Detection of the effects of phytoestrogens on sheep and cattle. J Anim Sci. 1995;73(5):1509-15. [PubMed] 
  70. Lee YH, Yuk HJ, Park KH, Bae YS. Coumestrol induces senescence through protein kinase CKII inhibition-mediated reactive oxygen species production in human breast cancer and colon cancer cells. Food Chem. 2013;141(1):381-8. [Crossref] [PubMed] 
  71. Liu S, Hsieh D, Yang YL, Xu Z, Peto C, Jablons DM, et al. Coumestrol from the national cancer Institute's natural product library is a novel inhibitor of protein kinase CK2. BMC Pharmacol Toxicol. 2013;14:36. [Crossref] [PubMed] [PMC] 
  72. Zafar A, Singh S, Naseem I. Cytotoxic activity of soy phytoestrogen coumestrol against human breast cancer MCF-7 cells: insights into the molecular mechanism. Food Chem Toxicol. 2017;99:149-61. [Crossref] [PubMed] 
  73. Hedelin M, Löf M, Olsson M, Adlercreutz H, Sandin S, Weiderpass E. Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women. J Nutr. 2008;138(5):938-45. [Crossref] [PubMed] 
  74. Klinge CM, Risinger KE, Watts MB, Beck V, Eder R, Jungbauer A. Estrogenic activity in white and red wine extracts. J Agric Food Chem. 2003;51(7):1850-7. [Crossref] [PubMed] 
  75. Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H. Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer. 2008;15(1):161-73. [Crossref]  [PubMed] 

.: Up To Date

.: Process List

Login



Contact


Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com