MUSTAFA KELEŞ, Mehmet GÜNDOĞDU, FUAT ERDEM, Mehmet TÜRKELİ, Leyla YILDIZ, Hamdullah TURHAN

Non-Hodgkin lenfomalı hastalarda IGF-1 ve IGFBP-3 düzeyleri

Amaç: İnsülin benzeri büyüme faktörü (IGF), bir çok kanser türünde kanser hücreleri için önemli bir büyüme ve antiapopitotik faktördür. İnsülin benzeri büyüme faktörü bağlayıcı protein-3 (IGFBP-3) ise IGF-1 den bağımsız apopitozisi uyarır ve büyümeyi inhibe eder. Bu çalışmada serum IGF- 1 ve IGFBP-3 düzeylerine bakmayı, sağlıklı kontrol ile karşılaştırmayı ve bazı prognostik faktörlerle ilişkilerini araştırmayı amaçladık. Gereç ve Yöntem: Hematoloji ve Onkoloji Bilim Dallarında non Hodgkin lenfoma (NHL) tanısı konan ve yaşları 18-63 (ortalama 40±16.19) arasında olan 25 olgu ile, 18-63 yaşları arasında olan 25 sağlıklı gönüllüden 8-10 ml venöz kan alındı. Santrifüj edilen kanların serumları ayrılarak çalışma gününe kadar -800C de derin dondurucuda bekletildi. Hasta ve kontrol serumlarından IGF-1 ve IGFBP-3 ölçümleri immunoflorasan assay (IFA) ve immunoradyometrik assay (IRMA) yöntemleri ile yapıldı. Bulgular: Hasta grubunun serum IGF-I düzeyi (357.88±197.45 ng/ml) kontrol grubuna (332.47±140.51 ng/ml) göre yüksek olmasına rağmen bu fark istatistiksel olarak anlamlı değildi (p>0.05). Hasta grubunun IGFBP-3 (1753.14±603.58 ng/ml) düzeyleri kontrol grubuna (1842.84±403.33 ng/ml) göre düşük olmasına rağmen bu fark da istatistiksel olarak anlamlı değildi (p>0.05). IGFBP-3 düzeyi B semptomu olan hastalarda (1577.35±582.52 ng/ml) B semptomu olmayanlara(2065.66±533.86 ng/ml) göre daha düşük olarak bulundu (p

Anahtar Kelimeler:

İnsülin-benzeri büyüme faktörü I, Lenfom, Hodgkin dışı, İmmünoradyometrik test, Floresans antikor tekniği, İnsülin-benzeri büyüme faktörü bağlayıcı protein 3

IGF-1 and IGFBP-3 levels in patients with non-Hodgkin’s lymphoma

Objectives: Insulin-like growth factor 1 (IGF-1) is an important growth and anti-apoptotic factor for the cancer cells in several malignancies. IGF binding protein-3 (IGFBP-3) also apparently inhibits growth and induces apoptosis through IGF-independent mechanisms. In this study it was aimed to measure serum IGF-1 and IGFBP-3 levels in 25 patients with non-Hodgkin’s lymphoma and to compare with these results to healthy controls, and it was also aimed association between these results and some prognostic factors. Materials and Methods: Twenty five patients with non-Hodgkin’s lymphoma (NHL) whose age ranging from 18-63 (mean ± SE 40 ± 16.19) and 25 healthy volunteer whose age ranging from 18 to 63 (mean ± SE 40 ± 16.27) were obtained in Hematology and Oncology Department. Blood samples were collected and separated serums stored in –800C until study. IGF-1 ve IGFBP-3 levels were measured with immunofluorescence assay (IFA) and immunoradiometric assay (IRMA) (respectively). Results: IGF-1 level was higher in patients with NHL (mean±SE;357.88±197.45 ng/ml) than in healthy volunteer group (332.47±140.51 ng/ml), but this difference was not statistically significance (p>0.05). IGFBP-3 level was lower in patients with NHL (mean±SE; 1753.14±603.58 ng/ml) than in healthy volunteer group (1842.84±403.33 ng/ml), but this difference was not statistically significance (p>0.05). IGFBP-3 level in patients with B symptoms (1577.35±582.52 ng/ml) was significantly lower than in patients without B symptoms (2065.66±533.86 ng/ml) (p<0.005). Conclusion: Although there was not any statistical significance, IGF-1 level was found increase and IGFBP-3 was found decrease in NHL patients when compared to healthy volunteer group. IGFBP-3 level in patients with B symptoms was significantly lower than in patients without B symptoms .

Keywords:

Insulin-Like Growth Factor I, Lymphoma, Non-Hodgkin, Immunoradiometric Assay, Fluorescent Antibody Technique, Insulin-Like Growth Factor Binding Protein 3,

PDF

___

1) Jerome L, Shiry L, Jones BL. Deregulation of the IGF axis in cancer: epidemiological evidence and potential therapeutic interventions. Endocr Relat Cancer 2003; 10: 561-578.
2) Fürstenberger G, Senn HJ. Insulin-like growth factors and cancer. Lancet Oncol 2002; 3: 298-302.
3) Giovannucci E. Insulin-like growth factor-I and their binding protein-3 and risk of cancer. Hormone Research 1999; 51: 34-41.
4) LeRoith D, Baserga R, Helman L, Charles T. Roberts Jr. Insulinlike Growth Factors and Cancer. Ann Intern Med 1995; 122: 54- 59.
5) Grimberg A, Cohen P. Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 2000; 183: 1-9.
6) Czech MP. Signal transmission by the IGF’s. Cell 1989; 59: 235- 238.
7) Wu X, Yu H, Amos C, Hong W, Spitz M. Joint effect of insulinlike growth factors and mutagen sensitivity in lung cancer risk. J Natl Cancer Inst 2000; 92: 737-743.
8) Harman SM, Metter EJ, Blackman MR, Landis PK, Carter HB. Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGFbinding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. J Clin Endocrinol Metab 2000; 85: 4258- 4265.
9) Wolk A, Mantzoros CS, Andersson SO, et al. Insulin-like growth factor I and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 1998; 90: 911-915.
10) Aksoy Y, Aksoy H, Bakan E, Atmaca AF, Akçay F. Serum insulin-like growth factor-I and insülin-like binding protein-3 in localized, metastasized prostate cancer and benign prostatic hyperplasia. Urol Int 2004; 72: 62-65.
11) Yu H, Spitz MR, Mistry J, Gu J, Hong, WK, Wu X. Plasma levels of insulin-like growth factor-I and lung cancer risk: a casecontrol analysis. J Natl Cancer Inst 1999; 91: 151-156.
12) Lukanova A, Lundin E, Toniolo P, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, Zeleniuch- Jacquotte A, Berrino F, Hallmans G, Riboli E, Kaaks R. Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int J Cancer 2002; 101: 549-554.
13) Ayabe T, Tsutsumi O, Sakai H, Yoshikawa H, Yano T, Kurimoto F, Taketani Y. Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocr J 1997; 44: 419-424.
14) Steller MA, Delgado CH, Bartels CJ, Woodworth CD, Zou Z. Overexpression of the insulin-like growth factor-1 receptor and autocrine stimulation in human cervical cancer cells. Cancer Res 1996; 56: 1761-1765.
15) Lee DY, Yang DH, Kang CW, Kim SJ, Joo CU, Cho SC, Kim JS. Serum Insulin-like Growth Factors (IGFs) and IGF Binding Protein (IGFBP)-3 in Patients with Gastric Cancer: IGFBP-3 protease activity induced by surgery. JKMS 1997: 12: 32-39.
16) Molica S, Vitelli G, Mirabelli R, et al. Serum insulin-like growth factor is not elevated in patients with early B-cell chronic lymphocytic leukemia but is still a prognostic factor for disease progression. Eur J Haematol 2006; 76: 51-57.
17) Çömlekçi A. Doku büyüme faktörleri ve eikozanoidler. İçinde: Kabalak T, Yılmaz C, Tüzün M (yazarlar). Endokrinoloji El Kitabı. İzmir: İzmir Güven Kitabevi, 2004: 45-59.
18) Reiter EO, Rosenfeld RG. Normal and aberant growth. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS (eds). Williams Textbook of Endocrinology. Philadelphia: Saunders, 2003: 1016- 1031.