Sedat ABUŞOĞLU, Ali ÜNLÜ, Gülsüm ABUŞOĞLU, Bahadır ÇETİN, Funda KOSOVA, Özgü Kemal BEKSAÇ

MEME KANSERİ OLAN HASTALARDA SERUM HOMOSİSTEİN DÜZEYLERİNİN ARAŞTIRILMASI

Giriş ve Amaç: Hastalıkların tanısında kullanabilmek amacıyla birçok molekül üzerinde bilimsel çalışmalar devam etmektedir. Bu moleküllerden bir tanesinin bile tanı amacıyla kullanılabilmesi, klinisyenler açısından hastalığın tanısının konmasında oldukça önemlidir. Homosistein ve arjinin de bu doğrultuda üzerinde çalışmaların yoğun olarak devam ettiği moleküllerdendir. Bu nedenlerle biz de, bu çalışmamızda meme hastalarının kan örneklerinin serumlarında homosistein ve arjinin düzeylerinde herhangi bir değişiklik olup olmadığını belirleyebilmeyi ve bunun meme kanseri ile ilişkisini açıklayabilmeyi amaçlamaktayız. Gereç ve Yöntemler: Selçuk Üniversitesi Tıp Fakültesi Biyokimya Metabolizma Laboratuvarında çalışmalarımız gerçekleştirilmiştir. Çalışmamıza 20 kontrol, 20 meme Ca, 20 metastaz hastası dahil edildi. Meme kanseri hastalarından alınan kan, biyokimyasal analiz yapılana kadar -80 ° C'de saklanmıştır. Alınan kan örneklerinden elde edilen serumlardan homosistein ve arginin seviyeleri ölçülmüştür Spektrofotometrede 470 nm'de protein seviyeleri ölçülmüştür. Homosistein seviyelerini ölçmek için NMRkütle spektrometresi kullanılmıştır. Bulgular: Yapılan değerlendirmede Kontrol grubuna göre meme Ca ‘li hastalarda Arginin, Arginin/ADMA, metastazlı hastalarda ise Homosistein seviyelerinde istatistiksel bir artış gözlenmiştir. Meme kanserli hata grubu, metastaz grubu ile karşılaştırıldığında ise, Homosistein seviyesi istatiksel olarak artarken, Arginin /ADMA seviyesi istatistiksel olarak azalmıştır. Sonuç: Elde ettiğimiz sonuçlara dayanarak, meme kanseri hastalarının tanı ve tedavileri sırasında bu markerlerın kullanılabileceği düşünülmektedir.

Anahtar Kelimeler:

Meme kanseri, Homosistein, Arginin, Sitrülin

Investigation of Serum Homocystein Levels in Patients with Breast Cancer

Objective: Scientific studies are continuing on many molecules in order to be used in the diagnosis of diseases. The fact that even one of these molecules can be used for diagnosis is very important for clinicians in diagnosing the disease. For this purpose, intensive studies continue on homocysteine and arginine. For these reasons, in this study, we aim to determine whether there is any change in homocysteine and arginine levels in the serum of blood samples of breast patients and to explain its relationship with breast cancer. Material Materials and Methods: We carried out our work in Selcuk University Faculty of Medicine Biochemistry Metabolism Laboratory. Our study included 20 controls, 20 breast Ca, 20 metastasis patients. Blood collected from breast cancer patients stored at -80 ° C until biochemical analysis is performed. Homocysteine and arginine levels measured in the sera obtained from the blood samples taken. The levels of proteins were measured at 470 nm in the NMRspectrophotometer. To measure homocysteine levels were injected into the mass spectrometer for chromatography. Results: In the evaluation, a statistical increase was observed in Arginine, Arginine / ADMA levels in patients with breast Ca, and Homocysteine levels in patients with metastases compared to the control group. When the breast cancer error group was compared with the metastasis group, the homocysteine level increased statistically, while the Arginine / ADMA level decreased statistically. Conclusion: Based on the results we obtained, it is thought that these markers can be used during the diagnosis and treatment of breast cancer patients.

Keywords:

Homocysteine and Arginine, Breast cancer, Cytrulin,

PDF

___

Gough M.S, Morgan, M.A, Mack, C.M, Darling, D.C, Frasier, L.M, et al., The ratio of arginine to dimethylarginines is reduced and predicts outcomes in patients with severe sepsis, Critical Care Medicine, 2011, 39(6), 1351-8. doi: 10.1097/CCM.0b013e318212097c.
Cooke, J.P, Tsao, P.S, Arginine: a new therapy for atherosclerosis? Circulation, 1997, 95, 311-312.
Lüscher, T, Noll, G, Is it all in genes…? Nitric oxide synthase and coronary vasospasm, Circulation, 1999, 99, 2855-2857.
Furchgott, R.F, Zawadzki, J.V, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature, 1980, 299, 373-376.
Palmer, R.M, Ashton, D.S, Moncada, S, Vascular endothelial cells synthesize nitric oxide from L-arginine, Nature, 1988, 333, 664-666.
Palmer, R.M, Ferrige, A.G, Moncada, S, Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor, Nature, 1987, 327, 524-526.
Prefumo, F, Thilaganathan, B, Whitley, G.S, First-trimester uterine artery resistance and maternal serum concentration of asymmetric dimethylarginine, Ultrasound Obstetric Gynecology, 2008, 31(2) , 153-157.
Ganguly, P, Alam, S.F, Role of homocysteine in the development of cardiovascular disease, Nutrition Journal, 2015, 10,14, 6.
Alvarez, R, Gonzalez, P, Batalla, A, Reguero J.A, Cubero, G, Hevia, S, et al., Association between the NOS3 (2786 T/C) and the ACE (I/D) DNA Genotypes and Early Coronary Artery Disease, Journal of Biology and Chemistry, 2001, 5, 343-348.
Vidal, M.J, Romero, J.C, Vanhoutte, P.M, Endothelium-derived relaxing factor inhibits rennin release, European Journal of Pharmacology, 1998, 14, 401-402.
Veli-Pekka, V, Tomi-Pekka, T, Reijo L, DDAH gene and cardiovascular risk, Vascular Medicine, 2005, 10, S45–48.
Aydın, M, Fatma Erdoğmuş, F, Armutçu, F, Yiğitoğlu, M.R, Metabolism of Asymmetric Dimethylarginine (ADMA), International Jornal of Basic Clinical Medicine, 2013,1(1) ,61-66.
Bilgic¸ O, Altınyazar, H.C, Baran, H, Unlu, A, Serum homocysteine, asymmetric dimethyl arginine (ADMA) and other arginine–NO pathway metabolite levels in patients with psoriasis, Archive of Dermatological Res, 2015, 307, 439–444.
Ishıda, M, Kakuta, T, Mıyakogawa, T, Tatsumı, R, Matsumoto, C, Fukagawa, M, Association between Asymmetric Dimethylarginine and Pentosidine in Dialysis Effluent of Peritoneal Dialysis Patients, Tokai Journal of Experimental Clinical Medicine, 2016, Vol. 41, No. 2, pp. 97-100,
Reddy, K.R.K, Dasari, C, Duscharla, D, Supriya, B, Sai, N, Ram, M. et al., Dimethylarginine dimethylaminohydrolase‑1 (DDAH1) is frequently upregulated in prostate cancer, and its overexpression conveys tumor growth and angiogenesis by metabolizing asymmetric dimethylarginine (ADMA), Angiogenesis, https://doi.org/10.1007/s10456-017-9587-0
Yüksel, E., , Ağır Sepsis Ve Septik Şoklu Hastalarda Asimetrik Dimetilarjinin (Adma) Ve Nitrik Oksit (No) Düzeylerinin Araştırılması, Gazi Üniversitesi Sağlık Bilimleri Enstitüsü, Yüksek Lisans Tezi, 2010, Ankara, 82 s.
Böger, R, Asymmetric dimethylarginine (ADMA): A novel risk marker in cardiovascular medicine and beyond, Annals of Medicine, 2006, 38, 126-136.
Clarke, S, Protein methylation, Current Opinion of Cell Biology, 1993, 5, 977–983.
McBride, A.E, Silver, P.A, State of the Arg: Protein methylation at arginine comes of age, Cell, 2001, 106, 5–8.
Alaçam, H, Dikmen, Z.G, Doğan, P, Asimetrik dimetil arjinin (ADMA) metabolizması ve ADMA’n›n oksidatif hasar, endotel hasarı ve çeşitli hastalıklarla ilişkisi, International Journal of Basic Clinic Medicine, 2010, 41, 75-81.
Taner, A, 2010, Diyabetik Hastalarda Maskeli Hipertansiyonun Gelişiminde Asimetrik Dimetil Argininin Rolü, Selçuk Üniversitesi Meram Tıp Fakültesi Tıbbi Biyokimya Anabilim Dalı, Uzmanlık Tezi, Konya, 69 s.
Holden, D.P, Cartwright, J.E, Nussey, S.S, Whitley, G.S, Estrogen stimulates dimethylarginin dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine Circulation, 2003,108,1575–1580.
Erdem, S, Ünlü, A, Asimetrik dimetilarjinin ve klinik önemi, Selçuk Tıp Dergisi, 2009, 25 (2), 107-115.
Arikan, E, Karadag, C.H, Guldiken, S, Asymmetric dimethylarginine levels in thyroid diseases, Journal Endocrinology Investigation, 2007, 30(3), 186-91.
Szuba, A, Chachaj, A, Wróbel, T, Dzietczenia, J, Mazur, G, Antonowicz-Juchniewicz, J, Kuliczkowski, K, Andrzejak, R, Asymmetric dimethylarginine in hematological malignancies: a preliminary study, Leukemia Lymphoma, 2008, 49(12), 2316-20.
Akyol, M, Kara, M, Alacacıoglu, A, Demır, L, Ellıdokuz, H, Kucukzeybek, Y, The Effects Of Adjuvant Chemotherapy On Serum Adma And Endothelın-1 Levels In Early Stage Breast Cancer Patıents (Izmır Oncology Group (Izog) Study, Acta Medica Mediterranea, 2017, 33, 557.