Atila EROĞLU, Fatma GENÇ, Yusuf BİLEN, Yener AYDIN, İbrahim KAPLAN, Mevlüt Sait KELEŞ

Özofagus kanserli olgularda plazma arginin, arginaz ve nitrik oksit seviyelerinin değerlendirilmesi

Amaç: Çeşitli kanserlerde plazma arginin, arginaz ve nitrik oksit (NO) ile ilgili birçok çalışma yapılmış ve buparametrelerin kanser hastaları için belirleyici faktörler olabileceği ileri sürülmüştür. Bu çalışmada özofagus kanserlihastalarda plazma arjinin, arjinaz ve nitrik oksit seviyeleri değerlendirildi.Yöntem ve gereç: Çalışmaya özofagus kanseri tanısı konup henüz opere edilmemiş 51’i kadın ve 49’u erkek olmak üzere100 hasta dahil edildi. Olguların yaş ortalamaları 62,03 ± 12,4 idi. Radyoterapi veya kemoterapi alan hastalar çalışmayadahil edilmedi. Yaş ortalamaları 57 ± 12,4 olan 38 kadın ve 42 erkek olmak üzere 80 bireyden oluşan kontrol grubuoluşturuldu. Olguların plazma arginin ve NO düzeyi ile arginaz aktivitesi ölçüldü. Arginin düzeyi yüksek performanslılikit kromatografi yöntemi, nitrik oksit düzeyi Griess reaksiyonuyla, arginaz aktivitesi ise modifi ye Geyer ve Dabichmetoduyla ölçüldü.Bulgular: Plazma arginin konsantrasyonu özofagus kanserli hastalarda kontrol grubuna oranla belirgin derecededüşük, nitrik oksit düzeyi ve arginaz aktivitesi ise kontrol grubuna oranla önemli derecede yüksek bulundu (sırasıyla P< 0,0001, P < 0,0001 ve P = 0,005). Arginaz ve nitrik oksitin sensitivitesi % 87 ve % 89, spesifi tesi ise % 65 ve % 66 olarakhesaplandı. Arginin, nitrik oksit düzeyleri ve arginaz aktivitesi, uzak organ metastazı olan hastalar ile metastaz olmayanhastalarla kıyaslandığında istatistiksel olarak anlamlı bir fark bulunmadı (P > 0,05). Benzer şekilde bu parametreler yassıepitel hücreli karsinom ve adenokarsinomalı hastalar ile kıyaslandığında da istatiksel olarak anlamlı bir fark saptanmadı(P > 0,05).Sonuç: Elde ettiğimiz sonuçlar özofagus kanserli hastaların tanısında plazma NO düzeyi ile arginaz aktivitesininbir tümör belirteci olarak kullanılabileceğini göstermektedir. Ancak bununla ilgili daha kapsamlı ve ileri düzeydeçalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

Özofagus kanseri, arginaz, arginin, nitrik oksit

The evaluation of plasma arginine, arginase, and nitric oxide levels in patients with esophageal cancer

Many studies have been conducted to investigate plasma arginine, arginase, and nitric oxide (NO) levels in patients with different types of cancer, and it has been suggested that these might be important factors for patients with cancer. In the present study, plasma arginine, arginase, and nitric oxide levels were evaluated in patients with esophageal cancer. Materials and methods: A total of 100 patients (51 females and 49 males) diagnosed with esophageal cancer but not yet operated on were included in the study. The mean age of the study population was 62.03 ± 12.4 years. Patients treated with radiotherapy or chemotherapy were excluded. The control group included 80 subjects (38 females and 42 males) with a mean age of 57 ± 12.4 years. Plasma arginine, NO levels, and arginase activity were measured. High-performance liquid chromatography, Griess reactions, and modified Geyer and Dabich methods were used to detect the arginine levels, NO levels, and arginase activity. Results: In patients with esophageal cancer, plasma arginine concentrations were significantly lower and NO levels and arginase activity were significantly higher than in the control groups (P < 0.0001, P < 0.0001, and P = 0.005, respectively). The sensitivity of arginase and NO were estimated at 87% and 89%, with respective specificities of 65% and 66%. Between the patients with and without distant organ metastasis, there were no significant differences in arginine/NO levels and arginase activity (P > 0.05). Similarly, there were no significant differences in these parameters between the patients with squamous cell carcinoma and adenocarcinoma (P > 0.05). Conclusion: The results demonstrate that plasma NO levels and arginase activity may be used as markers for the diagnosis of esophageal cancer. However, larger and more comprehensive studies are needed.

Keywords:

Key words: Esophageal cancer, arginase, arginine, nitric oxide,

PDF

___

Cheeseman KH. Mechanisms and eff ects of lipid peroxidation. Mol Aspects Med 1993; 14: 191-7.
Kurtuluş H, Eskiocak S, Tütüncüler F, Başaran ÜN, Gülen Ş. Deneysel sistemik hipoksi geliştirilmiş yenidoğan ratlarda N-asetilsistein uygulamasının etkileri [Th e eff ect of n-acetylcysteine administration on pups with neonatal hipoxia]. Turk J Biochem 2003; 28: 40-4 (in Turkish with English abstract). 3. Barış N, Turgan N, Ersoz B. Argininin tıpsal biyokimyadaki önemi [Th e signifi cance of arginine in medical biochemistry]. Türk Klinik Biyokimya Derg 2004; 2: 83-90 (in Turkish with English abstract).
Geyer JW, Dabich D. Rapid method for determination of arginase activity in tissue homogenates. Anal Biochem 1971; 39: 412-7.
Meram İ, Ahi S, Tarakçıoğlu M. Kanserde serum arginaz aktivitesi [Serum arginase activity in cancer]. Van Medicine Journal 2000; 7: 20-3 (in Turkish). 6. Moshage H, Kok B, Huizenga JR, Jansen PLM. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 1995; 41: 892-6.
Türkyılmaz A, Eroğlu A, Aydın Y, Karaoğlanoğlu N. Th e relationship of serum CEA and CA 19-9 levels to liver metastasis and pancreatic invasion in esophageal cancer. Turk J Med Sci 2009; 39: 895-9. 8. Rodriguez PC, Quiceno DG, Ochoa AC. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 2007; 109: 1568-73.
Van Eijk HMH, Dejong CHC, Deutz NEP, Soeters PB. Infl uence of storage conditions on normal plasma amino-acid concentrations. Clin Nutr 1994; 13: 374-80.
Lamb J, Wheatley DN. Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of cdk4 expression. Exp Cell Res 2000; 255: 238-49.
Hester JE, Fee WE. Eff ect of arginine on growth of squamous cell carcinoma in the CH3/KM mouse. Arch Otolaryngol Head Neck Surg 1995; 121: 193-6.
Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG et al. L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 2003; 171: 1232-9.
Naini AB, Dickerson JW, Brown MM. Preoperative and postoperative levels of plasma protein and amino acid in esophageal and lung cancer patients. Cancer 1988; 62: 355-60.
Chang CI, Liao JC, Kuo L. Macrophage arginase promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity. Cancer Res 2001; 61: 1100-6.
Leu SY, Wang SR. Clinical signifi cance of arginase in colorectal cancer. Cancer 1992; 70: 733-6.
Harris BE, Pretlow TP, Bradley EL Jr, Whitehurst GB, Pretlow TG 2nd. Arginase activity in prostatic tissue of patients with benign prostatic hyperplasia and prostatic carcinoma. Cancer Res 1983; 43: 3008-12.
Löser C, Fölsch UR, Paprotny C, Creutzfeldt W. Polyamine concentrations in pancreatic tissue, serum, and urine of patients with pancreatic cancer. Pancreas 1990; 5: 119-27.
Wu CW, Chi CW, Ho CK, Chien SL, Lui WY, P’Eng FK et al. Eff ect of arginase on splenic killer cell activity in patients with gastric cancer. Dig Dis Sci 1994; 39: 1107-12.
Chrzanowska A, Krawczyk M, Barańczyk-Kuźma A. Changes in arginase isoenzymes pattern in human hepatocellular carcinoma. Biochem Biophys Res Commun 2008; 377: 337-40.
Wu CW, Wang SR, Chang TJ, Lin EC, Chang KL, Huang MH et al. Content of glucocorticoid receptor and arginase in gastric cancer and normal gastric mucosal tissues. Cancer 1989; 64: 2552-6.
Gökmen SS, Yıldız R, Tabakoğlu E, Altıay G, Yavuz E, Gülen Ş. Akciğer kanserli hastalarda eritrosit arginaz aktivitesi [Erythrocyte arginase activity in lung cancer patients]. Trakya Univ Tip Fak Derg 2005; 22: 76-81. (in Turkish with English abstract).
Gökmen SS, Aygıt AC, Ayhan MS, Yorulmaz F, Gülen Ş. Signifi cance of arginase and ornithine in malignant tumors of the human skin. J Lab Clin Med 2001; 137: 340-4.
Morbidelli L, Donnini S, Ziche M. Role of nitric oxide in tumor angiogenesis. Cancer Treat Res 2004; 117: 155-67.
Radomski MW, Jenkins DC, Holms L, Moncada S. Human colorectal adenocarcinoma cells: diff erential nitric oxide synthesis determines their ability to aggregate platelets. Cancer Res 1991; 51: 6073-8.
Alexandrova R, Mileva M, Zvetkova E. Nitric oxide and cancer (minireview). Exp Pathol Parasitol 2001; 4: 13-8.
Yu J, Guo F, Ebert MPA, Malfertheiner P. Expression of inducible nitric oxide synthase in human gastric cancer. WJG 1999; 5: 430-1.
Martin JHJ, Alalami O, van den Berg HW. Reduced expression of endothelial and inducible nitric oxide synthase in a human breast cancer cell line which has acquired estrogen independence. Cancer Lett 1999; 144: 65-74.
Chen T, Nines RG, Peschke SM, Kresty LA, Stoner GD. Chemopreventive eff ects of a selective nitric oxide synthase inhibitor on carcinogen-induced rat esophageal tumorigenesis. Cancer Research 2004, 64; 3714-7.
Zidek Z, Masek K. Erratic behavior of nitric oxide within the immune system: illustrative review of confl icting data and their immunopharmacological aspects. Int J Immunopharmacol 1998; 20: 319-43.
Bing RJ, Miyataka M, Rich KA, Hanson N, Wang X, Slosser HD et al. Nitric oxide, prostanoids, cyclooxygenase, and angiogenesis in colon and breast cancer. Clin Cancer Res 2001; 7: 3385-92.