Turkiye Klinikleri Journal of Health Sciences

.: REVIEW
Kanserde Kaşeksi Patofizyolojisi ve Egzersizin Etkisi: Geleneksel Derleme
Cancer Cachexia Pathophysiology and Effect of Exercise: Traditional Review
Ezgi ERGİNa, Didem KARADİBAKb
aDokuz Eylül Üniversitesi Sağlık Bilimleri Enstitüsü, Fizyoterapi ve Rehabilitasyon Bölümü, İzmir, Türkiye
bDokuz Eylül Üniversitesi Fizik Tedavi ve Rehabilitasyon Fakültesi, Kardiyopulmoner Rehabilitasyon Bölümü, İzmir, Türkiye
Turkiye Klinikleri J Health Sci. 2023;8(3):536-44
doi: 10.5336/healthsci.2023-96712
Article Language: TR
Full Text
ÖZET
 Kanser kaşeksisi (KK); beslenme desteğiyle düzelmeyen, ilerleyici fonksiyonel bozulma, iskelet kas kütlesi kaybı ile karakterize çok faktörlü bir sendromdur ve ileri evre kanser hastalarında oldukça yüksek oranlarda görülmektedir. Prekaşeksi, kaşeksi ve refrakter kaşeksi olarak 3 evresi bulunmaktadır. Sistemik inflamasyon, tümör hücrelerinden proinflamatuar sitokin üretimiyle tetiklenmektedir. Sitokin üretiminin organlara yayılma etkisi akut faz yanıtı, katabolik-anabolik uyarı değişimleri, artmış enerji harcaması, azalmış enerji alımı, anoreksiya, insülin direnci, oksidatif stres artışı, mitokodriyal disfonksiyon, yağ dokusunda ve kasta kayıplara yol açmaktadır. KK'de çok faktörlü patofizyoloji nedeniyle kapsamlı değerlendirme yapılmalıdır. Değerlendirme, uygun tedavi planının belirlenmesinde oldukça önemlidir. Net bir tedavi planı bulunmamasına rağmen egzersizin etkili olabileceği belirtilmiştir. Yapılan hayvan çalışmalarında, aerobik egzersizin oksidatif kapasitede artma, tümör hacminde ve inflamasyonda azalma ve kas atrofisini önlemeyi sağladığı bulunmuştur. Dirençli egzersizin KK'li bireylerde güvenli ve uygulanabilir olduğu, hareketlilik, kas kuvveti ve yağsız vücut kütlesinde anlamlı artış sağladığı görülmüştür. Hayvan çalışmalarında dirençli egzersizin; inflamasyon ve hiperlipidemide azalma, kilo alımı ve protein sentezinde artma sağladığı bildirilmiştir. Yapılan hayvan çalışmalarında, aerobik ve direçli kombine egzersizin; protein katabolizması ve oksidatif streste azalma, kas kaybını önleme ve kas kütlesinde artma sağladığı belirtilmiştir. Egzersiz, umut verici ve farmakolojik olmayan bir yaklaşımdır ve KK'li bireylerde egzersizin etkilerinin incelendiği çalışmalara ihtiyaç vardır. Bu çalışmada, KK'nin patofizyolojisi, kullanılan değerlendirme yöntemleri ve egzersizin patofizyoloji üzerine etkilerinin derlenmesi amaçlamıştır.

Anahtar Kelimeler: Kanser; kaşeksi; patofizyoloji; egzersiz; egzersiz tedavisi
ABSTRACT
 Cancer cachexia (CC) is characterized by progressive functional deterioration and loss of skeletal muscle mass, which doesn't improve with nutritional support, and is seen at very high rates in advanced cancer patients. It has stages as precachexia, cachexia and refractory cachexia. Systemic inflammation is triggered by proinflammatory cytokines production from tumor cells. The effect of cytokine production spreading to organs causes acute phase response, catabolicanabolic stimulus changes, increased energy expenditure, decreased energy intake, anorexia, insulin resistance, increased oxidative stress, mitochodrial dysfunction, loss of muscle and adipose tissue. Because of the multifactorial pathophysiology in CC, comprehensive evaluation should be performed. Evaluation is significant in determining the appropriate treatment plan. Although there isn't clear treatment plan, exercise can be effective. Animal studies reported that aerobic exercise increases oxidative capacity, reduces tumor volume and inflammation and prevents muscle atrophy. Resistance exercise has been reported to be feasible and safe in individuals with CC, provides significant improvements in mobility, muscle strength and lean body mass. Animal studies, reported that resistance exercise reduces inflammation and hyperlipidemia, increases weight and protein synthesis. Animal studies, stated that aerobic and resistance combined exercise is effective in reducing protein catabolism and oxidative stress, preventing muscle loss and improving muscle mass. Exercise is a promising non-pharmacological approach and exercise studies are needed for CC in adults. This study aimed to review the pathophysiology, evaluation methods and the effects of exercise on the pathophysiology.

Keywords: Cancer; cachexia; pathophysiology; exercise; exercise therapy
REFERENCES:
  1. Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754-62. [Crossref]  [PubMed] 
  2. Anker MS, Holcomb R, Muscaritoli M, von Haehling S, Haverkamp W, Jatoi A, et al. Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review. J Cachexia Sarcopenia Muscle. 2019;10(1):22-34. [Crossref]  [PubMed]  [PMC] 
  3. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489-95. [Crossref]  [PubMed] 
  4. Seelaender M, Batista M Jr, Lira F, Silverio R, Rossi-Fanelli F. Inflammation in cancer cachexia: to resolve or not to resolve (is that the question?). Clin Nutr. 2012;31(4):562-6. [Crossref]  [PubMed] 
  5. Noguchi Y, Yoshikawa T, Marat D, Doi C, Makino T, Fukuzawa K, et al. Insulin resistance in cancer patients is associated with enhanced tumor necrosis factor-alpha expression in skeletal muscle. Biochem Biophys Res Commun. 1998;253(3):887-92. [Crossref]  [PubMed] 
  6. Li YP, Reid MB. NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes. Am J Physiol Regul Integr Comp Physiol. 2000;279(4):R1165-70. [Crossref]  [PubMed] 
  7. Laviano A, Meguid MM, Yang ZJ, Gleason JR, Cangiano C, Rossi Fanelli F. Cracking the riddle of cancer anorexia. Nutrition. 1996;12(10):706-10. [Crossref]  [PubMed] 
  8. Bonetto A, Aydogdu T, Kunzevitzky N, Guttridge DC, Khuri S, Koniaris LG, et al. STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS One. 2011;6(7):e22538. [Crossref]  [PubMed]  [PMC] 
  9. Brown JL, Rosa-Caldwell ME, Lee DE, Blackwell TA, Brown LA, Perry RA, et al. Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice. J Cachexia Sarcopenia Muscle. 2017;8(6):926-38. [Crossref]  [PubMed]  [PMC] 
  10. Tsai VW, Lin S, Brown DA, Salis A, Breit SN. Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15. Int J Obes (Lond). 2016;40(2):193-7. [Crossref]  [PubMed] 
  11. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab. 2004;287(4):E591-601. [Crossref]  [PubMed] 
  12. Nicolini A, Ferrari P, Masoni MC, Fini M, Pagani S, Giampietro O, et al. Malnutrition, anorexia and cachexia in cancer patients: a mini-review on pathogenesis and treatment. Biomed Pharmacother. 2013;67(8):807-17. [Crossref]  [PubMed] 
  13. Holroyde CP, Gabuzda TG, Putnam RC, Paul P, Reichard GA. Altered glucose metabolism in metastatic carcinoma. Cancer Res. 1975;35(12):3710-4. [PubMed] 
  14. Shellock FG, Riedinger MS, Fishbein MC. Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J Cancer Res Clin Oncol. 1986;111(1):82-5. [Crossref]  [PubMed] 
  15. Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B, et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science. 2011;333(6039):233-8. Erratum in: Science. 2011;333(6049):1576. [Crossref]  [PubMed] 
  16. Yeom E, Yu K. Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia. Exp Mol Med. 2022;54(4):426-32. [Crossref]  [PubMed]  [PMC] 
  17. Acharyya S, Ladner KJ, Nelsen LL, Damrauer J, Reiser PJ, Swoap S, et al. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest. 2004;114(3):370-8. [Crossref]  [PubMed]  [PMC] 
  18. Rausch V, Sala V, Penna F, Porporato PE, Ghigo A. Understanding the common mechanisms of heart and skeletal muscle wasting in cancer cachexia. Oncogenesis. 2021;10(1):1. [Crossref]  [PubMed]  [PMC] 
  19. Gioulbasanis I, Georgoulias P, Vlachostergios PJ, Baracos V, Ghosh S, Giannousi Z, et al. Mini Nutritional Assessment (MNA) and biochemical markers of cachexia in metastatic lung cancer patients: interrelations and associations with prognosis. Lung Cancer. 2011;74(3):516-20. [Crossref]  [PubMed] 
  20. Neelemaat F, Meijers J, Kruizenga H, van Ballegooijen H, van Bokhorst-de van der Schueren M. Comparison of five malnutrition screening tools in one hospital inpatient sample. J Clin Nurs. 2011;20(15-16):2144-52. [Crossref]  [PubMed] 
  21. Vigano AL, di Tomasso J, Kilgour RD, Trutschnigg B, Lucar E, Morais JA, et al. The abridged patient-generated subjective global assessment is a useful tool for early detection and characterization of cancer cachexia. J Acad Nutr Diet. 2014;114(7):1088-98. [Crossref]  [PubMed] 
  22. Thoresen L, Frykholm G, Lydersen S, Ulveland H, Baracos V, Prado CM, et al. Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results. Clin Nutr. 2013;32(1):65-72. [Crossref]  [PubMed] 
  23. Ellegård LH, Ahlén M, Körner U, Lundholm KG, Plank LD, Bosaeus IG. Bioelectric impedance spectroscopy underestimates fat-free mass compared to dual energy X-ray absorptiometry in incurable cancer patients. Eur J Clin Nutr. 2009;63(6):794-801. [Crossref]  [PubMed] 
  24. Dolan RD, Daly L, Sim WMJ, Fallon M, Ryan A, McMillan DC, et al. Comparison of the prognostic value of ECOG-PS, mGPS and BMI/WL: Implications for a clinically important framework in the assessment and treatment of advanced cancer. Clin Nutr. 2020;39(9):2889-95. [Crossref]  [PubMed] 
  25. Barker T, Fulde G, Moulton B, Nadauld LD, Rhodes T. An elevated neutrophil-to-lymphocyte ratio associates with weight loss and cachexia in cancer. Sci Rep. 2020;10(1):7535. [Crossref]  [PubMed]  [PMC] 
  26. Nozoe T, Ninomiya M, Maeda T, Matsukuma A, Nakashima H, Ezaki T. Prognostic nutritional index: a tool to predict the biological aggressiveness of gastric carcinoma. Surg Today. 2010;40(5):440-3. [Crossref]  [PubMed] 
  27. Blauwhoff-Buskermolen S, Ruijgrok C, Ostelo RW, de Vet HCW, Verheul HMW, de van der Schueren MAE, et al. The assessment of anorexia in patients with cancer: cut-off values for the FAACT-A/CS and the VAS for appetite. Support Care Cancer. 2016;24(2):661-6. [Crossref]  [PubMed]  [PMC] 
  28. Amano K, Morita T, Koshimoto S, Uno T, Katayama H, Tatara R. Eating-related distress in advanced cancer patients with cachexia and family members: a survey in palliative and supportive care settings. Support Care Cancer. 2019;27(8):2869-76. [Crossref]  [PubMed] 
  29. Miller J, Wells L, Nwulu U, Currow D, Johnson MJ, Skipworth RJE. Validated screening tools for the assessment of cachexia, sarcopenia, and malnutrition: a systematic review. Am J Clin Nutr. 2018;108(6):1196-208. [Crossref]  [PubMed] 
  30. Stout NL, Santa Mina D, Lyons KD, Robb K, Silver JK. A systematic review of rehabilitation and exercise recommendations in oncology guidelines. CA Cancer J Clin. 2021;71(2):149-75. [Crossref]  [PubMed]  [PMC] 
  31. Morishita S, Hamaue Y, Fukushima T, Tanaka T, Fu JB, Nakano J. Effect of exercise on mortality and recurrence in patients with cancer: a systematic review and meta-analysis. Integr Cancer Ther. 2020;19:1534735420917462. [Crossref]  [PubMed]  [PMC] 
  32. Daou HN. Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation. Am J Physiol Regul Integr Comp Physiol. 2020;318(2):R296-310. [Crossref]  [PubMed] 
  33. Ballarò R, Penna F, Pin F, Gómez-Cabrera MC, Vi-a J, Costelli P. Moderate exercise improves experimental cancer cachexia by modulating the redox homeostasis. Cancers (Basel). 2019;11(3):285. [Crossref]  [PubMed]  [PMC] 
  34. Tanaka M, Sugimoto K, Fujimoto T, Xie K, Takahashi T, Akasaka H, et al. Preventive effects of low-intensity exercise on cancer cachexia-induced muscle atrophy. FASEB J. 2019;33(7):7852-62. [Crossref]  [PubMed] 
  35. Olesen J, Kiilerich K, Pilegaard H. PGC-1alpha-mediated adaptations in skeletal muscle. Pflugers Arch. 2010;460(1):153-62. [Crossref]  [PubMed] 
  36. Grande AJ, Silva V, Sawaris Neto L, Teixeira Basmage JP, Peccin MS, Maddocks M. Exercise for cancer cachexia in adults. Cochrane Database Syst Rev. 2021;3(3):CD010804. [Crossref]  [PubMed]  [PMC] 
  37. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011;11(9):607-15. [Crossref]  [PubMed] 
  38. de Sousa CV, Sales MM, Rosa TS, Lewis JE, de Andrade RV, Simões HG. The antioxidant effect of exercise: a systematic review and meta-analysis. Sports Med. 2017;47(2):277-93. [Crossref]  [PubMed] 
  39. Sato S, Gao S, Puppa MJ, Kostek MC, Wilson LB, Carson JA. High-frequency stimulation on skeletal muscle maintenance in female cachectic mice. Med Sci Sports Exerc. 2019;51(9):1828-37. [Crossref]  [PubMed]  [PMC] 
  40. Gould DW, Lahart I, Carmichael AR, Koutedakis Y, Metsios GS. Cancer cachexia prevention via physical exercise: molecular mechanisms. J Cachexia Sarcopenia Muscle. 2013;4(2):111-24. [Crossref]  [PubMed]  [PMC] 
  41. Gholamian S, Attarzadeh Hosseini SR, Rashidlamir A, Aghaalinejad H. The effects of interval aerobic training on mesenchymal biomarker gene expression, the rate of tumor volume, and cachexia in mice with breast cancer. Iran J Basic Med Sci. 2020;23(2):244-50. [PubMed]  [PMC] 
  42. Puppa MJ, White JP, Velázquez KT, Baltgalvis KA, Sato S, Baynes JW, et al. The effect of exercise on IL-6-induced cachexia in the Apc ( Min/+) mouse. J Cachexia Sarcopenia Muscle. 2012;3(2):117-37. [Crossref]  [PubMed]  [PMC] 
  43. Lira FS, Yamashita AS, Rosa JC, Koyama CH, Caperuto EC, Batista ML Jr, et al. Exercise training decreases adipose tissue inflammation in cachectic rats. Horm Metab Res. 2012;44(2):91-8. [Crossref]  [PubMed] 
  44. Grote M, Maihöfer C, Weigl M, Davies-Knorr P, Belka C. Progressive resistance training in cachectic head and neck cancer patients undergoing radiotherapy: a randomized controlled pilot feasibility trial. Radiat Oncol. 2018;13(1):215. [Crossref]  [PubMed]  [PMC] 
  45. Kamel FH, Basha MA, Alsharidah AS, Salama AB. Resistance training impact on mobility, muscle strength and lean mass in pancreatic cancer cachexia: a randomized controlled trial. Clin Rehabil. 2020;34(11):1391-9. [Crossref]  [PubMed] 
  46. Galvão DA, Taaffe DR, Spry N, Joseph D, Newton RU. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol. 2010;28(2):340-7. [Crossref]  [PubMed] 
  47. Repka CP, Hayward R. Oxidative stress and fitness changes in cancer patients after exercise training. Med Sci Sports Exerc. 2016;48(4):607-14. [Crossref]  [PubMed]  [PMC] 
  48. Ranjbar K, Ballarò R, Bover Q, Pin F, Beltrà M, Penna F, et al. Combined exercise training positively affects muscle wasting in tumor-bearing mice. Med Sci Sports Exerc. 2019;51(7):1387-95. [Crossref]  [PubMed] 
  49. Niels T, Tomanek A, Schneider L, Hasan I, Hallek M, Baumann F. Exercise improves patient outcomes in advanced pancreatic cancer patient during medical treatment. Pancreat Disord Ther. 2018;8(1). [Crossref] 
  50. Karlsen T, Aamot IL, Haykowsky M, Rognmo Ø. High intensity interval training for maximizing health outcomes. Prog Cardiovasc Dis. 2017;60(1):67-77. [Crossref]  [PubMed] 

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

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