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      Evaluation of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 Expression Levels in Patients with Chronic Lymphocytic Leukemia Translated title: Kronik Lenfositik Lösemi Hastalarında İnsülin-benzeri Büyüme Faktörü-1 ve İnsülin-benzeri Büyüme Faktörü Bağlayıcı Protein-3 Düzeylerinin Değerlendirilmesi

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          Abstract

          Objective:

          Chronic lymphocytic leukemia (CLL) is a disease of nonproliferating and mature-appearing B lymphocytes. Insulin-like growth factor-1 (IGF-1) is a small peptide hormone and has mitogenic and antiapoptotic effects, and insulin-like growth factor binding protein-3 (IGFBP-3) has antiproliferative effects on cells. In this study, we investigated plasma levels of both IGF-1 and IGFBP-3 in patients with CLL compared with controls, and we compared these plasma levels according to prognostic factors.

          Materials and Methods:

          Patients with newly diagnosed CLL who were being followed at the Haseki Training and Research Hospital, İstanbul, Turkey, and volunteers were included in this study. Patients were stratified according to the Rai staging system. Statistical analysis was conducted using SPSS 17.0 for Windows.

          Results:

          Forty-three patients [16 women (37%) and 27 men (63%)] were enrolled in this study. Twenty-one volunteers (11 women, 10 men) were included in the control group. The median age of the patients was 65±9 years (range: 18-63 years), and subjects in the control group were 68±8 years old (range: 18-63 years). Even though the plasma levels of IGF-1 were higher and those of IGFBP-3 were lower and the ratio of IGF-I/IGFBP-3 was higher in comparison with the control group, these differences were not statistically significant (p>0.05). In the study group, IGF-1 levels appeared to be increased in parallel to more advanced Rai stages. There were no significant differences between the other groups (p=0.105).

          Conclusion:

          Plasma IGF-I levels were found higher in patients than in the control group and plasma IGFBP-3 levels were lower; however, neither result was statistically significant. Plasma IGF level increment was observed in concordance with Rai staging. These results prompted us to think that plasma IGF-1 levels in CLL patients are correlated with tumor burden and Rai staging and therefore could be a valuable prognostic factor. Further comprehensive studies are required to support our results.

          Translated abstract

          Amaç:

          Kronik lenfositik lösemi (KLL) olgun görünümlü B lenfositlerin hastalığıdır. İnsülin-benzeri büyüme faktörü-1 (IGF-1), mitojenik ve antiapoptotik etkili küçük peptid hormondur ve insülin-benzeri büyüme faktörü bağlayıcı protein-3 (IGFBP-3) ise hücre üzerinde antiproliferative etki gösterir. Çalışmamızda, KLL hasta grubu ve kontrol grubunda plazma IGF-1 ve IGFBP-3 düzeylerini ve prognostik faktörlerle ilişkisini karşılaştırdık.

          Gereç ve Yöntemler:

          Haseki Eğitim ve Araştırma Hastanesi, Hematoloji Bölümü’nde takip edilen yeni tanı almış KLL hastaları ile kontrol grubu çalışmaya dahil edilmiştir. Hastalar Rai sistemine göre evrelendirilmiştir. İstatistiksel analiz SPSS for Windows version 17.0 kullanılarak yapılmıştır.

          Bulgular:

          Kırk üç hasta [16 kadın (%37) ve 27 erkek (%63)] çalışmaya alınmıştır. Kontrol grubu 21 kişiden (11 kadın, 10 erkek) oluşmuştur. Hasta grubunda ortanca yaş 65±9 (18-63), kontrol grubunda 68±8’dir (18-63). Kontrol grubu ile karşılaştırıldığında; çalışma grubunda plazma IGF-1 düzeyi yüksek; IGFBP-3 düzeyi düşük, IGF-I/IGFBP-3 oranı ise yüksek olarak bulunmasına rağmen istatistiksel yönden anlamlı değildi (p>0,05). Çalışma grubunda plazma IGF-1 düzeyi yüksekliği ile Rai ileri evresi paralellik gösteriyordu. Diğer gruplarla istatistiksel yönden anlamlı farklılık yoktu (p=0,105).

          Sonuç:

          Çalışma grubunda, plazma IGF-1 düzeyi kontrol grubundan daha yüksek, IGFBP-3 düzeyi ise düşük bulundu, bununla beraber istatistiksel yönden anlamlı farklılık yoktu. Plazma IGF-1 düzeyi yüksekliği ile Rai ileri evresi uyumlu idi. Bu sonuçlar bize, IGF-1 düzeyinin KLL hastalarında tümor yükü ve Rai evresi ile ilişkili olduğunu ve prognostik faktör olarak değerli olabileceğini düşündürmüştür. Bu sonuçları destekleyebilmek için daha geniş kapsamlı çalışmalara ihtiyaç vardır.

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          Most cited references8

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          Induction of the growth inhibitor IGF-binding protein 3 by p53.

          Transcriptional activation of target genes represents an important component of the tumour-suppressor function of p53 and provides a functional link between p53 and various growth-regulatory processes, including cell cycle progression (p21/WAF1), DNA repair (GADD45) and apoptosis (bax). Here we use a differential cloning approach to identify the gene encoding insulin-like growth factor binding protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3 gene expression by wild-type but not mutant p53 is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may link p53 to potential novel autocrine/paracrine signalling pathways and to processes regulated by or dependent on IGF(s), such as cellular growth, transformation and survival.
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            Insulin-like growth factors and cancer.

            The insulin-like growth factor (IGF) family of peptides, binding proteins, and receptors are important for normal human growth and development and are involved in the specialized functions of most physiologic systems. Most members of the IGF system are expressed by different cancer cells and may play an important role in the propagation of these malignancies. New therapies aimed at modulating various components of the IGF system could affect the progression and metastasis of cancer.
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              Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer.

              Insulin-like growth factors (IGFs) may play a role in prostate growth, hyperplasia, and malignancy. High plasma IGF-I has been associated with increased prostate cancer risk. In a prospective, cohort, case-control study in the Baltimore Longitudinal Study on Aging population, we examined prostate volume by magnetic resonance imaging, and prostate-specific antigen (PSA), IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases (n = 72) or age-matched controls (n = 127) and in 76 additional Baltimore Longitudinal Study on Aging men (normal subjects) with measured prostate volumes and no prostate cancer. We calculated adjusted odds ratios (OR) by logistic regression, relative risks for significant ORs, and receiver operator curves for prostate cancer, using serum measures alone and in combination. Adjusted ORs for the high vs. low tertile were: for IGF-I, 3.1 [confidence interval (CI), 1.1-8.7]; for IGF-II, 0.2 (CI, 0.07-0.6); for IGFBP-3, 0.71 (CI, 0.3-1.7); and for PSA, 12.5 (CI, 3.8-40.9). For significant ORs, relative risk estimates remained significant at 2.0 for IGF-I, 0.3 for IGF-II, and 5.5 for PSA. Receiver operator curves showed PSA to be the most powerful predictor of prostate cancer. Adding IGF-II to PSA improved prediction. IGF-II was significantly and inversely related (r = -0.219; P < 0.01) and PSA was directly and significantly related (r = 0.461; P < 0.0001) to prostate volume, whereas IGF-I and IBFBP-3 were not. High IGF-I and low IGF-II are independently associated with increased risk of prostate cancer, but PSA level is a much stronger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II. The absence of a relationship of IGF-I to prostate size is inconsistent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest that IGF-II may inhibit both prostate growth and development of prostate cancer.
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                Author and article information

                Journal
                Turk J Haematol
                Turk J Haematol
                TJH
                Turkish Journal of Hematology
                Galenos Publishing
                1300-7777
                1308-5263
                December 2016
                1 December 2016
                : 33
                : 4
                : 335-338
                Affiliations
                [1 ] Haseki Training and Research Hospital, Clinic of Hematology, İstanbul, Turkey
                [2 ] Okmeydanı Training and Research Hospital, Clinic of Internal Medicine, Oncology Unit, İstanbul, Turkey
                [3 ] Haseki Training and Research Hospital, Clinic of Internal Medicine, İstanbul, Turkey
                [4 ] İstanbul University İstanbul Faculty of Medicine, Department of Internal Medicine, Division of Hematology, İstanbul, Turkey
                Author notes
                * Address for Correspondence: Haseki Training and Research Hospital, Clinic of Hematology, İstanbul, Turkey Phone: +90 212 529 44 00/2048 E-mail: mesutayerdr@ 123456hotmail.com
                Article
                1852
                10.4274/tjh.2016.0075
                5204190
                27094973
                6e5dc134-d96f-4ab1-8fe2-a63fa00c2108
                © Turkish Journal of Hematology, Published by Galenos Publishing.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2016
                : 8 April 2016
                Categories
                Brief Report

                chronic lymphocytic leukemia,insulin-like growth factor-1,insulin-like growth factor binding protein-3

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