scholarly journals IGFBP-4: A promising biomarker for lung cancer

2021 ◽  
Vol 40 (3) ◽  
pp. 237-244
Author(s):  
Savas Nur ◽  
Akin Ozturk ◽  
Murat Kavas ◽  
Ismet Bulut ◽  
Sumeyye Alparslan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Protein A ◽  
Serum Levels ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Healthy Individuals ◽  
Treatment Status ◽  
Patient Groups ◽  
Lung Cancer Biomarker

Background: Insulin-like growth factor binding protein-4 (IGFBP-4), a member of the insulin-like growth factor (IGF) family, transports, and regulates the activity of IGFs. The pregnancy-associated plasma protein-A (PAPP-A) has proteolytic activity towards IGFBP-4, and both proteins have been associated with a variety of cancers, including lung cancer. Thus, we aimed to evaluate the use of IGFBP-4 and PAPP-A as potential biomarkers for lung cancer. Methods: Eighty-three volunteers, including 60 patients with lung cancer and 23 healthy individuals, were included in this study. The patients with lung cancer were selected based on their treatment status, histological subgroup, and stage of the disease. Enzyme-linked immunosorbent assays were used to assess the serum levels of IGFBP-4 and PAPPA, whereas the IGF-1 levels were measured using a chemiluminescent immunometric assay. Results: The serum IGFBP-4 levels in all patient groups, regardless of the treatment status and histological differences, were significantly higher than those in the control group (p < 0.005). However, the serum PAPP-A levels in the untreated patient group were found to be higher than those in the control group, but this difference was not statistically significant (p = 0.086). Conclusions: The serum PAPP-A and IGFBP-4 levels are elevated in lung cancer. However, IGFBP-4 may have better potential than PAPP-A as a lung cancer biomarker.

scholarly journals SAT-046 Insulin-Like Growth Factor and Fibroblast Growth Factor 21 in Men with Klinefelter Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Simon Chang ◽  
Rikke Hjortebjerg ◽  
Anders Bojesen ◽  
Mette Bjerre ◽  
Claus Hojbjerg Gravholt
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Klinefelter Syndrome ◽  
Protein A ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Fibroblast Growth ◽  
Igf System

Abstract Background: Men with 47, XXY Klinefelter syndrome (KS) commonly present with obesity, metabolic disorders, and insulin insensitivity. The insulin-like growth factor (IGF) system has pleiotropic effects including regulation of glucose metabolism. Fibroblast growth factor 21 (FGF21) is associated with weight loss and favourable metabolic changes, but patients with obesity or type 2 diabetes might be resistant to this effect despite presenting with increased levels. Aim: To describe levels of components in the IGF system and FGF21 among men with KS, either treated or not treated with testosterone supplementation therapy (TT), in comparison with control males. Methods: A total of 66 men with KS were included, 33 without current TT and 33 with current TT. A control group of 70 healthy age-matched males were included. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP3), pregnancy-associated plasma protein A (PAPP-A), FGF21, and fibroblast activation protein (FAP) were compared between the three groups applying the Kruskal-Wallis test. Results: Levels of (IGF-1 µg/L) were not different between the groups (median (25-75 %), untreated KS 162 (140-201.5), treated KS 165 (128.5-215), controls 176.5 (150.8-214.5), p=0.5). Similarly, FGF21 levels (ng/L) were comparable between the groups (median (25-75 %), untreated KS 84.7 (53.3-217.6), treated KS 97.2 (56.4-224.8), controls 100.3 (66.0-191.0), p=0.9). Levels of IGFBP3, PAPP-A and FAP were also found to be comparable between the groups (p≥0.2). Conclusion: This was the first study investigating FGF21 in men with KS. Our results indicate that regulation of the IGF-1 system and levels of FGF21 are not altered in men with KS compared with age-matched controls, and that TT in men with KS does not affect these systems.

The effects of adenoidectomy of serum insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children with otitis media with effusion

2020 ◽  
Vol 74 (4) ◽  
pp. 13-17
Author(s):  
Beata Żelazowska-Rutkowska ◽  
Klaudia Jacewicz ◽  
Edwina Kasprzycka ◽  
Bożena Skotnicka ◽  
Bogdan Cylwik
Keyword(s):  
Growth Factor ◽  
Otitis Media ◽  
Otitis Media With Effusion ◽  
Reference Group ◽  
Serum Insulin ◽  
Serum Levels ◽  
Control Group ◽  
Healthy Children ◽  
Insulin Like Growth Factor ◽  
Significant Difference

<b>Aim:</b> The aim of the current study was to assess the serum levels of insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children suffering with or without otitis media with effusion before and after adenoidectomy. <br><b>Material and methods:</b> Serum IGF-1 and ghrelin concentrations were measured with specific enzyme-linked immunoassay (ELISA) methods. The study was carried out in 20 children with otitis media with effusion. The reference group comprised 24 children with hypertrophied adenoid, while control group included 19 children. <br><b>Results:</b> This mean values of IGF-1 in children with otitis media with effusion and children with hypertrophied adenoid before adenoidectomy were significantly lower than those found in healthy children. Serum levels of IGF-1 were higher after adenoidectomy. There was a significant difference of serum ghrelin levels between both examined groups and the control group. <br><b>Conclusion:</b> Our results suggest that adenoidectomy in children with hypertrophied adenoids and in children with otitis media with effusion significantly increases the level of IGF-1 in serum compared to before surgery through the effect of the GH-IGF-1 axis, which could contribute to children’s growth.

scholarly journals A Dietary Intervention to Lower Serum Levels of IGF-I in BRCA Mutation Carriers

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 309 ◽  
Author(s):  
Patrizia Pasanisi ◽  
Eleonora Bruno ◽  
Elisabetta Venturelli ◽  
Daniele Morelli ◽  
Andreina Oliverio ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dietary Intervention ◽  
Brca Mutation ◽  
Intervention Group ◽  
Serum Levels ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Mutation Carriers ◽  
Igf I ◽  
Brca Mutation Carriers

Background: Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might influence the penetrance of BRCA gene mutation. In a demonstration project on BRCA mutation carriers we tested the effect of the ‘Mediterranean diet’, with moderate protein restriction, on serum levels of IGF-I and IRm. Methods: BRCA mutation carriers, with or without breast cancer, aged 18–70 years and without metastases were eligible. After the baseline examinations, women were randomized to an active dietary intervention or to a control group. The intervention group attended six full days of life-style intervention activities (cookery classes followed by lunch, sessions of walking for 45 min and nutritional conferences) over the next six months. Results: 213 BRCA mutation carriers completed the six-month study. Women in the intervention group (110) showed major changes in all the parameters under study. They significantly lost weight (p < 0.001), fat mass (p = 0.002), with reduced hip circumference (p = 0.01), triglycerides (p = 0.02) and IGF-I (p = 0.02) compared with controls. They also had a significantly higher levels of insulin-like growth factor-binding protein 3 (IGFI-BP3) (p = 0.03) and a lower IGF-I/IGFI-BP3 ratio (p = 0.04). The reduction of serum levels of IGF-I was significantly associated with the reduction in the consumption of animal products (p = 0.04). Conclusions: Women in the intervention group showed significant improvements in IGF-I and in other IRm that might influence the penetrance of BRCA mutations.

scholarly journals Serum Resistin and Insulin-Like Growth Factor-1 Levels in Patients with Hypothyroidism and Hyperthyroidism

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Ceren Eke Koyuncu ◽  
Sembol Turkmen Yildirmak ◽  
Mustafa Temizel ◽  
Tevfik Ozpacaci ◽  
Pinar Gunel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Enzyme Linked Immunosorbent Assay ◽  
Insulin Like Growth Factor ◽  
Healthy Individuals ◽  
Control Groups ◽  
Chemiluminescence Method ◽  
And Control ◽  
Hyperthyroid Patients

Introduction. The aim of this study was to evaluate the serum levels of resistin and insulin-like growth factor-1 (IGF-1) and and also the potential relationship between thyroid function and levels of resistin and IGF-1 in hypothyroid and hyperthyroid patients.Methods. Fifteen cases of hypothyroid (HT), 16 of subclinically hypothyroid (SCHT), 15 of hyperthyroid (HrT), 15 of subclinically hyperthyroid (SCHrT), and 17 healthy individuals have been included in the study. Serum resistin levels were measured using enzyme-linked immunosorbent assay and IGF-1 and thyroid stimulating hormone (TSH) levels by chemiluminescence method.Results. Resistin levels in total HT group were significantly higher than in controls (12.66 ± 6.04 and 8.45 ± 2.90 ng/mL, resp.). In SCHrT subgroup resistin levels were significantly higher than those of controls (14.88 ± 7.73 and 8.45 ± 2.90 ng/mL, resp.). IGF-1 levels were significantly lower in total HT than in total HrT and control groups (117.22 ± 52.03, 155.17 ± 51.67, and 184.00 ± 49.73 ng/mL, resp.). Furthermore IGF-1 levels in HT subgroup were significantly lower compared to controls (123.70 ± 44.03 and 184 ± 49.73 ng/mL, resp.). In SCHT subgroup IGF-1 levels were significantly lower than those of control and SCHrT groups (111.11 ± 59.35, 184.00 ± 49.73, and 166.60 ± 47.87 ng/mL, resp.). There were significant correlations between IGF-1 and TSH in HT subgroup and between resistin and TSH in total HrT group.Conclusion. It was concluded that increased resistin levels are directly related to thyroid dysfunction, and GH/IGF-1 axis is influenced in clinically or subclinically hypothyroidism patients.

Long-term treadmill training ameliorates endothelium-dependent vasorelaxation mediated by insulin and insulin-like growth factor-1 in hypertension

2015 ◽  
Vol 119 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Yi-Yuan Lin ◽  
Shin-Da Lee ◽  
Chia-Ting Su ◽  
Tsung-Lin Cheng ◽  
Ai-Lun Yang
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Treadmill Training ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Hypertensive Rats ◽  
Protein Levels ◽  
Significant Difference ◽  
Nos Inhibitors

Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.

scholarly journals Studies on regulation of IGF (insulin-like growth factor)-binding protein (IGFBP) 4 proteolysis by pregnancy-associated plasma protein-A (PAPP-A) in cells treated with phorbol ester

2004 ◽  
Vol 379 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Arun S. SIVANANDAM ◽  
Subburaman MOHAN ◽  
Hirohito KITA ◽  
Sanjay KAPUR ◽  
Shin-Tai CHEN ◽  
...  
Keyword(s):  
Growth Factor ◽  
Proteolytic Activity ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Fold Reduction ◽  
Sds Page ◽  
Eosinophil Major Basic Protein

PAPP-A (pregnancy-associated plasma protein-A) is produced by hSFs (human skin fibroblasts) and hOBs (human osteoblasts) and enhances the mitogenic activity of IGFs (insulin-like growth factors) by degradation of IGFBP-4 (insulin-like growth factor-binding protein 4). PKC (protein kinase C) activation in these cells led to reduction in IGFBP-4 proteolysis. This study was undertaken to determine the mechanism by which activation of PKC suppresses IGFBP-4 proteolysis. Treatment of hSFs/hOBs with TPA (PMA; 100 nM) reduced IGFBP-4 proteolysis without significantly decreasing the PAPP-A level in the CM (conditioned medium). Immunodepletion of the proform of eosinophil major basic protein (proMBP), a known PAPP-A inhibitor, from CM of TPA-treated cells (TPA CM) failed to increase IGFBP-4 proteolytic activity. Transduction of hSFs with proMBP retrovirus increased the concentration of proMBP up to 30 ng/ml and led to a moderate reduction in IGFBP-4 proteolysis. In contrast, TPA treatment blocked IGFBP-4 proteolysis but failed to induce a detectable amount of proMBP in the CM. While proMBP overexpression led to the formation of a covalent proMBP–PAPP-A complex and reduced the migration of PAPP-A on SDS/PAGE, TPA treatment dose- and time-dependently increased the conversion of a ≈470 kDa PAPP-A form (PAPP-A470) to a ≈400 kDa PAPP-A form (PAPP-A400). Since unreduced PAPP-A400 co-migrated with the 400 kDa recombinant PAPP-A homodimer and since PAPP-A monomers from reduced PAPP-A470 and PAPP-A400 co-migrated on SDS/PAGE, conversion of PAPP-A470 to PAPP-A400 is unlikely to be caused by proteolytic cleavage of PAPP-A. Consistent with the data showing that the increase in the ratio of PAPP-A400/PAPP-A470 is correlated with the extent of reduction in IGFBP-4 proteolysis, partially purified PAPP-A400 exhibited a 4-fold reduction in IGFBP-4 proteolytic activity compared with PAPP-A470. These data suggest that a novel mechanism, namely conversion of PAPP-A470 to the less-active PAPP-A400, could account for the TPA-induced suppression of PAPP-A activity.

scholarly journals Insulin-Like Growth Factor Bioactivity, Stanniocalcin-2, Pregnancy-Associated Plasma Protein-A, and IGF-Binding Protein-4 in Pleural Fluid and Serum From Patients With Pulmonary Disease

2017 ◽  
Vol 102 (9) ◽  
pp. 3526-3534 ◽  
Author(s):  
Ulrick Skipper Espelund ◽  
Mette Bjerre ◽  
Rikke Hjortebjerg ◽  
Torben Riis Rasmussen ◽  
Anders Lundby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pleural Fluid ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf Binding ◽  
Stanniocalcin 2 ◽  
Igf Binding Protein

Abstract Context Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective To compare activity and concentrations of IGF system components in pleural fluid and blood. Design Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66.7 to 81.9 years. Methods IGF-related proteins and cytokine levels were measured by immunoassays or immunoblotting. Bioactive IGF was measured by an IGF-1 receptor phosphorylation assay. Results Total IGF-1 concentration did not differ between the compartments, but concentrations of free IGF-1 and bioactive IGF were more than threefold higher in pleural fluid than in corresponding serum samples (P = 0.0004), regardless of etiology. Median pregnancy-associated plasma protein-A (PAPP-A) and interleukin (IL)-6 levels were increased 47-fold and 143-fold, respectively, in pleural fluid compared with plasma (P &lt; 0.0001). PAPP-A and IL-6 concentrations correlated positively (r = 0.46; P = 0.02). In pleural fluid, levels of PAPP-A–generated IGF binding protein-4 fragments correlated inversely with that of stanniocalcin-2 (r ≤ −0.42; P ≤ 0.05), a PAPP-A inhibitor; such correlations were absent in plasma. Conclusion Pathological pleural fluid is characterized by increased in vitro IGF bioactivity and elevated concentrations of PAPP-A, an IGF-activating proteinase. Thus, the tissue activity of the IGF system may differ substantially from that of the circulating IGF system. The correlation between IL-6 and PAPP-A indicates that inflammation plays a role in promoting local tissue IGF activity.

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