IGFBP-3 Research Articles

Birth weight, working memory and epigenetic signatures in IGF2 and related genes: a MZ twin study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

IGF2BP1: a novel IGH translocation partner in B acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Detecting and characterizing recurrent translocations is critical for ALL diagnosis and treatment. IGH (immunoglobulin heavy chain) rearrangements are relatively common in lymphoproliferative disorders, including ALL. Here we report a 16-year-old boy who was diagnosed with B acute lymphoblastic leukemia. Chromosome analysis showed a t(14;17)(q32;q21) with an additional copy of the derivative chromosome 14. IGH rearrangement was confirmed by concurrent FISH analysis. Chromosomal microarray analysis (CMA) showed the breakpoint at the 5 prime end of the IGF2BP1 gene located at 17q21.32. To the best of our knowledge, this is the first report of ALL with a 14;17 translocation resulting in an IGH-IGF2BP1 fusion; however, previous studies have implicated a role for up-regulation of IGF2BP1 in ALL.

Quantifying mRNA coding growth genes in the maternal circulation to detect fetal growth restriction

To examine whether mRNA circulating in maternal blood coding genes regulating fetal growth are differentially expressed in (1) severe preterm fetal growth restriction (FGR) and (2) at 28 weeks' gestation in pregnancies destined to develop FGR at term. mRNA coding growth genes were measured in 2 independent cohorts. The first was women diagnosed with severe preterm FGR (<34 weeks' gestation; n = 20) and gestation matched controls (n = 15), where the mRNA was measured in both maternal blood and placenta. The second cohort was a prospective longitudinal study (n = 52) of women whom had serial ultrasound assessments of fetal growth. mRNA coding growth genes in maternal blood were measured at 28 and 36 weeks in pregnancies with declining growth trajectories (ending up with term FGR; n = 10 among the 52 recruited) and controls who maintained normal growth trajectory (n = 15). In women with severe preterm FGR, there was increased expression of placental growth hormone (6.3-fold), insulin-like growth factors (IGF1, 3.4-fold; IGF2, 5.0-fold), IGF receptors (2.1-fold) and IGF binding proteins (3.0-fold), and reduced expression of ADAM12 (0.5-fold) in maternal blood (and similar trends in placenta) compared with controls (P < .05). Notably, at 28 weeks' gestation there was increased IGF2 (3.9-fold), placental growth hormone (2.7-fold), and IGF BP2 (2.1-fold) expression in maternal blood in women destined to develop FGR at term (P < .05). Measuring mRNA coding growth genes in maternal blood may detect unsuspected severe preterm FGR already present in utero, and predict term FGR when measured at 28 weeks' gestation.

IGF-1 and IGFBP-3 in the safety and efficacy of growth hormone treatment

Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency(GHD),and has achieved satisfactory effect.Growth hormone (GH) can stimulate liver cells to produce insulin-like growth actor(IGF-1) which mediated GH growth promoting effect.The majority of IGF-1 combine with insulin like growth factor binding protein 3.IGF-I promotes cell mitotic and inhibit cell apoptosis,in recent years,some scholars have reported that there is a certain relationship between IGF-1 and tumor occurrence and development,and thus leading to the attention to the efficacy and safety of rhGH treatment. Key words: Insulin like growth actor 1 ; Insulin like growth factor binding protein 3 ; Growth hormone; Treatment

Investigation of the differential gene expressions in neural tube defects through retinoic acid induction

Objective To investigate the differential gene expressions in neural tube defects by retinoic acid induction.Methods This study used the retinoic acid (RA)-induced neural tube defects (NTDs) model,which extracts all the RNA of normal nerve tissues and nerve tissues in mice with NTDs.Then,using a medium density chip containing more than 1 100 known genes,a comparison of the differential gene expressions in the normal embryo and the same period NTDs neural tube organizations within 9.5 days and 10.5 days was carried out.Finally,this study verified some of the differentially expressed genes by Northern hybridization.Results 8 differentially expressed genes in E9.5d,E10.5d phases of the two-point showed consistent changes,while NeK7,IGFBP5,ZW10,Csf3r,PSMC6,Cdk5,Rb1 showed downward changes in dealing with RA-induced NTDs group and Apoa-4 in RA Addressed to deal with NTDs group showed upward changes.Conclusions Multiclass genes are involved in the process of the occurrence of NTDs.The research is helpful for the understanding of molecular mechanisms in normal neural formation. Key words: Neural tube defects; Neurulation; Gene chip; Retinoic acid

Çocuklarda kronik adenotonsiller hipertrofinin büyüme üzerine etkilerinin adenotonsillektomi öncesi ve sonrası dönemde değerlendirilmesi

Aim: Several factors including genetic factors nutrition and environment play a critical role in the growth of children Adenotonsillar hypertrophy ATH can cause growth retardation by obstructing the upper airway Surgical treatment of ATH has been considered to have a positive effect on growth The aim of this study was to evaluate the role of chronic ATH on growth by measuring weight height body mass index BMI bone age serum insulin like growth factor 1 IGF 1 and insulin like growth factor binding protein 3 IGFBP 3 values before and after adenotonsillectomy Material and Method: The study was approved by the Ethics Committee 4 5 2004; 04 170 and written informed consents were obtained from parents of the participants A total of 40 prepubertal children who were diagnosed as chronic ATH were enrolled Obstructive symptoms were questioned in the medical history before surgery Weight height BMI and bone age values were measured and compared with reference values Preoperative serum IGF 1 and IGFBP 3 values were compared with the control group which consisted of healthy children Rates of obstructive symptoms weight height BMI bone age serum IGF 1 and IGFBP 3 values of the patients were determined seven months after adenotonsillectomy and were compared with preoperative values Results: Obstructive symptoms in children with ATH decreased remarkably after surgery Preoperative mean value of bone age of the patients was statistically lower than reference values p lt;0 05 and mean value of serum IGF 1 was lower than than the control group p lt;0 05 IGF 1 and IGFBP 3 values did not increase significantly after surgery p gt;0 05 However growth retardation was detected in three out of 40 patients based on the anthropometric measurements Conclusions: In this study antropometric findings showed that chronic ATH did not cause significant growth retardation in prepubertal children In addition we could not prove that surgical treatment of ATH improved the growth in the postoperative follow up period of seven months This result may be related with our study population with a limited number of patients who had baseline growth retardation and short postoperative follow up period Further studies with large number of patients and longer postoperative follow up periods are required to determine the exact role of chronic ATH in growth retardation Turk Arch Ped 2012; 47: 260 6

Study on intermittent hypoxia in children sleep apnea hypopnea syndrome model and insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels in serum

Using rats fed in intermittent hypoxia environment to study the relationship between sleep apnea hypopnea syndrome (SAHS) of children and growth retardation. The hypoxic chamber was designed and manufactured, the control of intermittent hypoxia was achieved. Twenty-four rats were randomly divided into three groups: mild and severe hypoxia group, and control group. In control group, the animals were normally fed, without interruption. The animals in other two groups were kept in the cabin, simulated mild and severe intermittent hypoxia conditions 8-hour a day, a total of 35 days. According to the results of preliminary experiments, the concentration of intermittent hypoxia and frequency were determined. The animals with mild hypoxia events occurred nearly six times per hour, the average minimum oxygen saturation dropped to 0.853, the animals with severe hypoxia events occurred nearly 24 times per hour, the average minimum oxygen saturation dropped to 0.776. Body mass and length were measured before and after experiment. The serum insulin-like growth factor (IGF)-1 and insulin-like growth factor binding protein (IGFBP)-3 expression were tested from venous blood by enzyme-linked immunosorbent assay (ELISA). The length and body mass of rats in three groups before and after experiment were not statistically different (P>0.05). Before the experiment the serum IGF-1 and IGFBP-3 levels were not significantly different (P>0.05). 35 d after the experiment, the serum IGF-1 (x±s, the same below) in the control group, mild hypoxia and severe hypoxia were (60.0±18.5) ng/ml, (40.6±9.9) ng/ml and (13.1±8.6) ng/ml, F=25.840, P<0.01; the serum IGFBP-3 were (1.93±0.23) µg/ml, (1.39±0.30) µg/ml and (0.90±0.21) µg/ml, F=33.929, P<0.01. The differences were statistically significant. The IGF-1 and IGFBP-3 levels decreased as the hypoxia increased (P<0.05). In simulated sleep apnea hypopnea syndrome, the intermittent hypoxia in young rats does not show physical growth retardation, but the serum IGF-1, IGFBP-3 levels decreased with the increase of hypoxia and decline of oxygen saturation.

Effects of a daily mixed nutritional supplement on physical performance, body composition, and circulating anabolic hormones during 8 weeks of arduous military training

The aim of this work was to investigate the effect of a daily mixed nutritional supplement upon body composition, physical performance, and circulating anabolic hormones in soldiers undergoing arduous training. Thirty males received either a habitual diet alone (CON, n = 15) or with the addition of a daily mixed supplement (SUP, n = 15) of ∼5.1 MJ·d⁻¹ during 8 weeks of training. Body composition (DEXA), maximal dynamic lift strength (MDLS), and vertical jump (VJ) were assessed, and resting blood samples were collected before and after training. Blood analysis included insulin-like growth factors (IGF-1, IGF BP-1, and IGF BP-3), testosterone, and cortisol. There were no group differences at baseline. Body mass loss (mean ± SD) (CON 5.0 ± 2.3, SUP 1.6 ± 1.5 kg), lean mass loss (CON 2.0 ± 1.5, SUP 0.7 ± 1.5 kg), and fat mass loss (CON 3.0 ± 1.6, SUP 0.9 ± 1.8 kg) were significantly blunted by SUP. CON experienced significant decrements in MDLS (14%), VJ (10%), and explosive leg power (11%) that were prevented by SUP. Military training significantly reduced circulating IGF-1 (28%), testosterone (19%), and the testosterone:cortisol ratio (24%) with no effect of SUP. Circulating IGF BP-1 concentration and cortisol remained unchanged throughout, although SUP abolished the significant decrease in circulating IGF BP-3 (20%) on CON. In conclusion, a daily mixed nutritional supplement attenuated decreases in body mass and lean mass and prevented the decrease in physical performance during an arduous military training program.

Abstract A57: Randomized double-blind trial of a rational combination of anthocyanins and curcumin for colon cancer prevention in subjects with colorectal adenomas: MIRACOL study

Abstract Rationale: Colorectal cancer (CRC) is one of the most frequent malignant neoplasms in both sexes within developed countries. Colorectal carcinogenesis is a multistage process that occurs over a period of 10–20 years. Colorectal adenomas (CA) are well recognized CRC risk markers. Evidence from epidemiological studies and clinical trials, suggests that removal of CA decreases the incidence of CRC, supporting the hypothesis that regression or elimination of CA through chemopreventive strategies would also reduce CRC's incidence. Inflammation and oxidative stress appear to play a crucial role in the development of CRC; NF-kB activation has been associated with multiple pathways of oncogenesis, including apoptosis, cell cycle control, differentiation, angiogenesis and cell migration; interference with these mechanisms may represent a strategy in CRC chemoprevention. Anthocyanins and curcumin represent, so far, the two most reliable candidates mainly due to their integrated capacity of modulating key steps of inflammatory processes, cell proliferation and tumor progression. Anthocyanins are a group of natural occurring pigments responsible for the red-blue color of many fruits and vegetables and are provided with remarkable antiproliferative, apoptogenic, antiinflammatory and antioxidant effects and with the capacity of inhibiting tumor progression in experimental models of gastrointestinal cancerogenesis. In a recent pilot study in CRC patients, anthocyanins administered for 7 days were dose-dependently effective in reducing the proliferation index Ki-67. Curcumin is a polyphenolic compound obtained from turmeric (Curcuma longa L.) endowed with marked anti-inflammatory, antioxidant and antineoplastic effects; due to its peculiar proximal carbonyls, curcumin is also effective in interacting with the intracellular redox status contributing to modulate main steps of cellular activation and proliferation. In the present study, we propose to test a rational combination of a natural enriched source of anthocyanins from bilberry (Vaccinium myrtillus L.), MIRTOSELECT© (standardized to contain 36 % anthocyanins) with a bioavailable form of curcumin, MERIVA©. Based on previous experience in humans, the proposed daily dosages of 1g of MIRTOSELECT© and 1g of MERIVA© would assure an effective concentration of anthocyanins and curcumin in the target tissue; and at plasmatic level. Design: To assess the effects of MIRTOSELECT© and MERIVA© on cell proliferation in both adenomatous and unaffected colonic tissue, we designed a presurgical, double blind, placebo-controlled, randomized phase I/II trial in patients with colorectal adenomatous polyps. After a complete colonoscopy and biopsy of the index polyp, 100 subjects with histologically confirmed CA will be assigned (50 per arm) to either placebo or MIRTOSELECT© 1g/d + MERIVA© 1gr/die treatment for 4–6 weeks before polyp removal. Primary endpoint will be the nuclear transcriptional activation marker β-Catenin in adenoma tissue in subjects treated with the complex compared with placebo. The study is designed to have 85% power to detect an absolute difference of 10% between arms in β-Catenin expression levels in adenoma tissue after treatment, assuming 10% lost to follow-up. Secondary endpoints include treatment modulation of biomarkers of oxidative activation (NF-kB), proliferation and apoptosis (Ki67, TUNEL), phlogosis (u-CRP), circulating IGFs (IGF-1, IGFBP-3), genetic expression profile and tolerability. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A57.

Allele-specific transcriptional elongation regulates monoallelic expression of the IGF2BP1 gene

BackgroundRandom monoallelic expression contributes to phenotypic variation of cells and organisms. However, the epigenetic mechanisms by which individual alleles are randomly selected for expression are not known. Taking cues from chromatin signatures at imprinted gene loci such as the insulin-like growth factor 2 gene 2 (IGF2), we evaluated the contribution of CTCF, a zinc finger protein required for parent-of-origin-specific expression of the IGF2 gene, as well as a role for allele-specific association with DNA methylation, histone modification and RNA polymerase II.ResultsUsing array-based chromatin immunoprecipitation, we identified 293 genomic loci that are associated with both CTCF and histone H3 trimethylated at lysine 9 (H3K9me3). A comparison of their genomic positions with those of previously published monoallelically expressed genes revealed no significant overlap between allele-specifically expressed genes and colocalized CTCF/H3K9me3. To analyze the contributions of CTCF and H3K9me3 to gene regulation in more detail, we focused on the monoallelically expressed IGF2BP1 gene. In vitro binding assays using the CTCF target motif at the IGF2BP1 gene, as well as allele-specific analysis of cytosine methylation and CTCF binding, revealed that CTCF does not regulate mono- or biallelic IGF2BP1 expression. Surprisingly, we found that RNA polymerase II is detected on both the maternal and paternal alleles in B lymphoblasts that express IGF2BP1 primarily from one allele. Thus, allele-specific control of RNA polymerase II elongation regulates the allelic bias of IGF2BP1 gene expression.ConclusionsColocalization of CTCF and H3K9me3 does not represent a reliable chromatin signature indicative of monoallelic expression. Moreover, association of individual alleles with both active (H3K4me3) and silent (H3K27me3) chromatin modifications (allelic bivalent chromatin) or with RNA polymerase II also fails to identify monoallelically expressed gene loci. The selection of individual alleles for expression occurs in part during transcription elongation.

Correlation of senile hip fracture type with expressions of insulin-like growth factor and its binding proteins

Objective To study the expression difference of the insulin-like growth factor-I (IGF-I)and IGF-binding proteins-3,4,5(IGFBP-3,4,5)in the peripheral and local areas in senile hip fracture and discuss the correlation between the expression and the fracture types. Methods The study involved the senile patients (over 65 years) with hip fractures to compare the expressions of peripheral and local IGF-I and IGFBP-3,4,5 and observe the correlation between expression and fracture type.Results The serum and local specimens of 46 patients were collected,with lower level of BMD,IGF-I and IGFBP-3,5 in the intertrochanteric fracture group than the femoral neck fracture group(P<0.001)and with higher level of serum and local IGFBP-4 in the intertrochanteric fracture group than the femoral neck fracture group (P<0.001).Only local IGFBP-4 mRNA had positive correlation with serum markers (R=0.544,P<0.001). Conclusions The expression difference of IGF-I and IGFBP in the peripheral and local serum may be one of pathogenesis leading to different types of hip fractures.Except for the IGFBP-4,the other factors may affect the bone metabolism of the senile hip fractures through different regulatory mechanisms. Key words: Hip fractures; IGF-I; IGFBP-3,4,5

Abstract A69: Randomized, presurgical study of allopurinol vs. placebo in subjects with colorectal adenomas

Abstract Rationale: Colorectal adenomas are well recognized colorectal cancer (CRC) risk markers, and regression of adenomas through chemopreventive strategies may reduce the incidence of CRC. Inflammation and oxidative stress appear to play a crucial role in the development of CRC, and interference with the mechanisms inducing oxidative stress and possibly cancer progression may represent a new strategy in CRC chemoprevention. Colonic cancerous tissue contains high levels of reactive oxygen metabolites (ROM), which may play an important role in the pathogenesis of CRC, and the effects of ROM scavengers are presently being tested for CRC chemoprevention. Allopurinol, a structural analogue of hypoxanthine inhibiting the action of xantine oxidase (XO), is a ROM scavenger largely employed as an anti-gout agent in clinical practice. Allopurinol use is highly safe, with very uncommon adverse events. Allopurinol was shown to increase survival of patients with advanced CRC, and a recent population-based case-control study showed that its use for at least 5 years was correlated with a diminished risk of developing CRC (Odds Ratio=0.33; 95% CI=0.16-0.71, Rennert G et al. AACR 3rd International Conference on Frontiers in Cancer Prevention Research 2004, Abstract #C88) after adjustment for other known risk factors. Design: To assess the effects of allopurinol on cell proliferation in both adenomatous and unaffected colonic tissue, we designed a randomized phase I/II, double blind, placebo-controlled, multicenter trial in patients with colorectal adenomatous polyps. After a complete colonoscopy and biopsy of the index polyp, subjects with histologically confirmed adenomas were assigned to either placebo or two doses of allopurinol (100mg or 300mg) and treated for 4-6 weeks before polyp removal. Samples of normal colonic tissue were also collected on both baseline and end-of-study colonoscopy. Treatment effect on cell proliferation was assessed by measuring changes of Ki-67 labeling index (primary endpoint: Ki-67 %change) on both adenomatous and normal colonic tissue. We calculated a total of 75 subjects (25 per arm), required (α = 0.05, 1-β = 0.85, one-sided test) to show a 27% to 40% reduction in Ki-67 LI depending on standard deviation of Ki-67. Secondary endpoints included treatment modulation of biomarkers of oxidative activation (NF-Kb and β-catenin), apoptosis (topoisomerase-II-α, Cox-3, Bcl-2), inflammation (u-CRP) and of circulating IGFs (IGF-1, IGFBP-3). Preliminary results: The first patient entered the study on May 13th 2006 and the last on May 31th, 2010, for a total study enrolment duration of about 4 years. Enrolment stopped on July 1, 2010, with a total of 73 subjects enrolled. An interim analysis performed on November 2008 (48 patients enrolled, mean age 62 yrs, mean BMI 25kg/m2) showed a 98% treatment compliance, with only 3 G1 adverse events (1 leg cramps, 1 erythema and 1 skin rush), confirming the high safety of allopurinol. Ki-67 analysis on the first 13 subjects enrolled showed a favourable trend: median Ki-67 expression in normal tissue doubled on placebo compared with a 5% increase in both treatments arms; in adenomas, it increased by 70% on placebo compared with 6% and 12% in the 100 mg and 300 mg allopurinol arm, respectively. Tissue and serum biomarker analyses on all subjects enrolled are underway and further results will be presented at the conference. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A69.

Abstract ED05-04: Presurgical models to effectively screen preventive agents

Abstract ED05-04: Presurgical models to effectively screen preventive agents

Effect of growth hormone on features of IGF-I-II-IGFBP3 pathway in pancreatic cancer

Objective To investigate the effect of GH on proliferation of pancreatic cancer cells and observe the features of IGF-IGFBP3 pathway in the host after GH administration. Methods Pancreatic cancer cells (SW-1990,PANC-1 and P3) during exponential growth stage were harvested and cultured in medium containing growth hormone (50 ng/ml). After 24, 48 and 72 hours, cells were counted using a Coulter Counter. Thirty-five Athymic nude Balb/c mice were inoculated with SW-1990cells. When tumors became palpable after inoculation, animals were randomized to receive GH points (1 h, 2 h, 6 h, 24 after the last injection), plasma samples were gathered for subsequent ELISA determination and liver was rapidly incised for immune blotting analysis. Results The results revealed that GH stimulated cell growth in vitro. GH elevated levels of IGF-Ⅰ , Ⅱ at the 1st , 2nd , 6th hour after the last injection. GH augmented the expression of IGFBP3 in the liver of the host in vivo (1 h, 2 h, 6 h, 24 h, respectively). Conclusion Such proteins as IGF- Ⅰ and Ⅱ might be associated with mechanism of last effect of GH on tumor host. The up-regulation of IGFBP3 by GH administration in the host may help to explain the phenomena that GH doesn't accelerate growth of pancreatic tumor in vivo. Key words: Pancreatic neoplasms; Growth hormone; Insulin-like growth factor-Ⅰ; Insulin-like growth factor-Ⅱ; Insulin-like growth factor binding proteino-3

199 IGFBP-3 promoter methylation activates the PI3K/Akt intracellular signaling pathway in CDDP resistant cell lines

Trabajo presentado al 21th Meeting of the European Association for Cancer Research celebrado en Bruselas (Belgica) del 25 de Junio al 30 de Junio de 2010.

266: Fetal growth in diabetic pregnancy: role of insulin like growth factor 1 and its binding protein IGF BP3

266: Fetal growth in diabetic pregnancy: role of insulin like growth factor 1 and its binding protein IGF BP3

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy

Objective. To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET).Methods. Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET.Results. There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET.Conclusions. Maternal IGF-2 has a significant positive correlation with PET.

Association of insulin, insulin-like growth factor and insulin-like growth factor binding proteins with the risk of colorectal cancer

To study the association of the changes of serum insulin, insulin-like growth factor (IGF-1), insulin-like growth factor binding proteins(IGFBPs), body mass index (BMI), waist and hip circumference ratio(WHR) with the genesis of colorectal cancer. Sera from 244 colorectal cancer patients before operation, 371 patients after operation and 150 healthy subjects were assayed for insulin, leptin, IGF-1, IGFBP-1 and IGFBP-3 by the enzyme-linked immunosorbent assay. SPSS 13.0 statistics software was applied to analyze the data. The serum levels of insulin, IGF-1 and the ratio of IGF-1/ IGFBP-3 in colorectal cancer patients before and after surgical treatment were significantly higher than those in controls. The serum levels of IGFBP-3 in patients before and after operation were significantly lower than those in controls, and the differences were significant(P=0.015,P=0.001, respectively). The BMI in colorectal carcinoma patients was not significantly different to the healthy controls(P>0.05). The WHR in colorectal carcinoma patients was higher than that in healthy subjects, and the difference was significant(P=0.003, P=0.035 respectively). The WHR in colon cancer patients was different to that in rectal cancer patients(P=0.046). The WHR and BMI in colon carcinoma patients were positively correlated with the serum insulin level and the value of IGF/IGFBP3. The WHR and BMI were negatively correlated with IGFBP3. The WHR and BMI were not correlated with IGF-1 and IGFBP1. The serum insulin, IGF-1 levels and the value of IGF-1/IGFBP-3 are significantly increased in colorectal cancer patients, and serum IGFBP-3 level is markedly decreased, which may be related to the genesis of colorectal cancer, but are not correlated with the progress and improvement of colorectal cancer. Central adipositas may be a risk factor for the genesis of colon cancer.

Serum Insulin-Like Growth Factor-1 and Nitric Oxide Levels in Parkinson's Disease

The aim of this study was to investigate the role of circulating growth hormone (GH), insulin growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and nitric oxide (NO) concentrations in the patients suffering from Parkinson's disease (PD). The study groups were consisted of 25 patients with PD and 25 matched healthy subjects as a control. The NO level of patients in PD group (2.3 ± 0.4 μmol/L) was significantly lower than that in the control group (2.8 ± 0.6 μmol/L) (P:.011). Although there were no statistically significant differences in the GH, IGF-1, and IGF BP-3 levels among the two groups, in this preliminary study, we found low NO and mildly elevated IGF-1 levels in the patients with PD. The results may be associated with adaptation or protective mechanisms in the neurodegenerative disease processes such as seen in the PD. Further studies should be carried out to confirm our results.

Serum cord-blood IGF-I and IGF BP-3 concentrations in relation to fetal maturity and birth weight in healthy neonates

UENPS.294 Serum cord-blood IGF-I and IGF BP-3 concentrations in relation to fetal maturity and birth weight in healthy neonates Stanislaw Pajak, Jakub Behrendt, Urszula Godula-Stuglik⁎ NICU, Department of Pediatrics, Silesian Medical University, Zabrze, Poland