Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients

SUMMARY OBJECTIVE: The aim of this study was to investigate the levels of leptin, growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 and their relations with clinical parameters in patients with primary fibromyalgia and healthy controls. METHODS: Our study was performed on 30 female patients with primary fibromyalgia and 30 healthy controls. The levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by a two-site immunoradiometric assay. The serum level of leptin was measured by the ELISA kit. RESULTS: The serum level of leptin was significantly higher, but the serum levels of insulin-like growth factor-1 were significantly lower in patients with fibromyalgia syndrome than healthy controls (p<0.001). The leptin level was positively correlated with the Visual Analog Scale, Fibromyalgia Impact Questionnaire score, Beck Depression Inventory score, tender point count, age, and duration of disease (p<0.001), but it was negatively correlated with insulin-like growth factor-1 (p<0.001). The insulin-like growth factor-1 level was negatively correlated with age, Visual Analog Scale, Fibromyalgia Impact Questionnaire and Beck Depression Inventory scores, duration of disease, and tender point count (p<0.001). CONCLUSION: Our results indicate that high levels of serum leptin and low levels of serum insulin-like growth factor-1 may play a role in the physiopathogenesis of fibromyalgia and may be related to some symptoms.

Gallbladder cancer-associated fibroblasts promote the migration of lymphatic endothelial cells via releasing IGFBP3 / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of gallbladder cancer-associated fibroblasts (CAFs) on the migration of lymphatic endothelial cells (LECs) so as to elucidate the molecular mechanisms involved. 【Methods】 The CAFs and normal fibroblasts (NFs) were extracted by enzymatic digestion, and the supernatant (CM) of CAFs and NFs was collected. The levels of IL-6, IGFBP3 and other related cytokines were detected by semi-quantitative protein factor microarray and ELISA. The expressions of α-SMA (CAFs maker) and IGFBP3 in gallbladder cancer and para-cancer tissues were detected by immunohistochemistry, and the correlation of α-SMA and IGFBP3 expressions with clinicopathological characteristics were analyzed. LECs were cultured and divided into serum-free medium group (control group), CAF-CM co-culture group, NF-CM co-culture group, IGFBP3 group, and CAF-CM+IGFBP3 inhibitor (2-Deoxy-D-glucose, 2-DG) group according to different treatment. Transwell migration assays and wound healing assays were applied to analyze the migration ability of LECs under different treatment. The expressions of E-cadherin, N-cadherin and Vimentin were detected by Western blotting. 【Results】 Protein factor microarray and ELISA showed that the concentration of IGFBP3 in CAF-CM was significantly increased, and the expression of α-SMA was significantly related to lymph node metastasis, advanced TNM stage and expression of IGFBP3. IGFBP3 secreted from CAF-CM significantly promoted LECs migration, up-regulated the expression of N-cadherin and Vimentin, and down-regulated the expression of E-cadherin. Treatment with IGFBP3 inhibitor 2-DG could reverse the effect of CAF-CM on migration of LECs and related protein expressions. 【Conclusion】 Gallbladder CAFs promote the migration of LECs via releasing IGFBP3, which affects EMT transformation.

Study on Genetic Polymorphism of IGFBP-3 Gene in Egyptian Buffalo

Aim: The present work was carried out to study the genetic characteristics of the IGFBP-3 gene in buffaloes reared in Egypt, where it is considered as one of the important molecular markers for productivity traits like growth and immunity in livestock species. One-hundred animals were used in this research work. Methods: The studied gene was amplified through polymerase chain reaction technique. Afterwards, the amplified fragment at 651-bp was digested with three different endonucleases; HaeIII, MspI, and TaqI. The genetic character of the IGFBP-3 gene was studied by using PCR-RFLP and nucleotide sequencing. Results: The PCR products after the digestion with those restriction enzymes revealed that the presence of the following fragments: two fragments at 506- and 145-bp with MspI two fragments at 240- and 411-bp with TaqI; and eight fragments at 199-, 164-, 154-, 56-, 36-, 18-, 16- and 8-bp with HaeIII. The restriction digestion of the amplified fragments of the IGFBP-3 gene did not show a genetic polymorphism or nucleotide substitution where all restricted fragments yielded from the digestion with three restriction enzymes were of the same sizes. Conclusion: Our findings indicated that the absence of the genetic polymorphism of the IGFBP-3 gene in Egyptian buffalo. Based on our results in addition to the significant effect of this gene on different productivity traits, the crossing between Egyptian buffalo with other breeds, particularly the Italian breed, is needed for more improvements of Egyptian buffalo's productivity where the Italian buffaloes characterized by high growth and fertility phenomena.

Effects of aerobic exercise plus diet control on serum levels of total IGF-1 and IGF-1 binding protein-3 in female obese youths and adolescents / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of 4-week moderate aerobic exercise plus diet control on serum levels of total insulin-like growth factor 1(IGF-1) and IGF-1 binding protein-3 (IGFBP-3) as well as IGF-1 activity (reflected by molar ratio of IGF-1/IGFBP-3) in female obese adolescents and youths, and their possible role on fat loss, and improvement of glucose and lipid metabolism.@*METHODS@#Nine female obese youths (age:18~19 y) and 30 female obese adolescents (age:14~16 y) were recruited and undertook 4-week aerobic exercise such as swimming and jogging (6 days/week, twice a day, 2 h/time with 5 min rest per 30 min exercise) with gradual increase of intensity from low (heart rate immediately post-exercise of 1st week:100~120 beats/min) to moderate (heart rate immediately post-exercise of 2-4 weeks:120~140 beats/min) level, combined with a diet intervention (total daily energy intake of 1 400 or 1 600 kcal according to basal metabolism rate) in Shanghai Dianfeng weight loss enclosed camp. Nine normal weight young women and 9 female children matched at age and nationality were recruited as the normal control. Before and after the experimental period, anthropometric index (body weight, body mass index(BMI) and waist circumference), glucose and lipid metabolism parameters including fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride (TG); total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL), and serum levels of total IGF-1 and IGFBP-3 were measured, and IGF-1 activity was calculated in the obese and normal control female adolescents.@*RESULTS@#①Compared with normal control, the serum levels of total IGF-1 and IGFBP-3 were decreased in the female obese youths and adolescents, and IGF-1 activity was reduced only in the obese female adolescents. ②The serum level of IGFBP-3 was down-regulated and IGF-1 activity was up-regulated while no change of serum total IGF-1 was induced by 4-week moderate aerobic exercise plus diet control, accompanied with significant decreases of body weight, BMI and waist circumference as well as improvement of glucose and lipid metabolism in the female obese youths and adolescents. Except for a positive association between the increased IGF-1 activity and the decreased waist circumference was found in the female obese youths by Pearson's correlation analysis, there was no relation of the decreased IGFBP-3, the increased IGF-1 activity with the improvements of anthropometric index and glucose and lipid metabolism in female obese youths and adolescents.@*CONCLUSIONS@#The serum level of IGFBP-3 was down-regulated and the IGF-1 activity was up-regulated by 4-week moderate aerobic exercise plus diet control in female obese youths and adolescents. The increase of IGF-1 activity might be associated with the exercise-plus-diet-induced decrease of waist circumstance in female obese youths.

The expression and significance of IGFBP-3 in salivary gland pleomorphic adenoma / 实用口腔医学杂志

Objective:To investigate the expression of insulin-like growth factor binding protein 3 (IGFBP-3) in salivary pleomorphic adenoma(SPA).Methods:The expression of IGFBP-3 protein in 40 cases of SPA(group SPA),40 of normal glandular tissue(group N) and 10 of salivary gland malignant tumor(group CA) was detected by Western blot.The expression of IGFBP-3 mRNA in 50 cases of SPA,50 of salivary gland normal tissue and 10 of CA was detected by qRT-PCR.Results:The expression(A value) of IGFBP-3 protein in group N,SPA and CA was 8.54 ± 3.95,4.78 ± 2.07,3.63 ± 2.27 respectively.The expression ration of IGFBP-3 mRNA of group N vs SPA or CA,P ＜ 0.05;SPA vs CA,P ＞ 0.05 (SPA/N was 0.654 ± 0.387,CA/N:0.452 ± 0.229) respectively,but showed no significance difference between SPA and the CA groups(P ＞ 0.05).Difference of IGFBP-3 mRNA expression was observed with different envelope infiltration of SPA (P ＜ 0.05),no significant difference was observed in different age,gender or relapse groups.Conclusion:IGFBP-3 Low expression of IGFBP-3 in pleomorphic adenomas may reduce the antagonism of IGF-1R,causing the proliferation of tumor cells and promote tumor formation.

Effects of IGFBP2 and IGFBP3 expression in ovarian tumors on migration, invasion of ovarian cancer / 中国比较医学杂志

Objective To study the effect on ovarian tumor migration invasion after inhibition the expression of IGFBP2, IGFBP3.Methods siRAN interference IGFBP2, IGFBP3 expression in ovarian cancer cell lines SKOV3, SKOV3 proliferation detected by CCK-8 kits,SKOV3 apoptosis detected by flow cytometry ,SKOV3 migration and invasion detected by transwell experiment and scratched cell healing detection; CCK-8 method detected survival after treated different concentrations of cisplatin (5, 10, 15, 20 ug/mL).Results The proliferation ability of SKOV3 dropped and apoptosis increased after treated siRAN IGFBP 2, IGFBP3 compared with the control group , migration and invasion function decline, resistance level to improve greatly.Conclusions The expression of IGFBP2, IGFBP3 in ovarian cancer affected migration and invasion .

Study on IGF-1 and IGFBP-3 gene expression in liver of young rats with intermittent hypoxia / 临床耳鼻咽喉头颈外科杂志

Objective:Using the model of young rats with intermittent hypoxia, to study the expression of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in liver, and to provide objective evidence for the possible existence of growth retardation in children with OSAHS. Method:Divided 24 rats randomly into three groups, as control group and the mild and severe hypoxia group. Normally fed control group, without treatment, the other two groups were kept in the cabin has been simulated mild and severe intermittent hypoxia conditions of OSAHS in children. 8-hour day cycle of intermittent hypoxia, a total of 35 days. To the last day, animals were sacrificed and fresh liver tissues were fixed in liquid nitrogen, stored in the -80°C refrigerator, then took the molecular biology experiment of IGF-1 and IGFBP-3 in the liver. Result:The expression of IGF-1 mRNA in liver, semi-quantitative analysis showed that the difference of mRNA expression of IGF-1 among the three groups was statistically significant (P<0.05), pairwise comparison, mild hypoxia group was higher than control and severe group, there were significant differences (P<0.05), the control group and severe hypoxia had no significant difference (P>0.05). The expression of IGFBP-3 mRNA in liver showed that, differences between the three groups was not significant (P>0.05). IGF-1 expression in liver tissue analysis showed that, differences between the three groups was statistically significant (P<0.05), pairwise comparisons, its expression in the control group was lower than mild hypoxia group and severe group, there were significant differences (P<0.05), mild hypoxia and severe hypoxia group had no significant difference (P>0.05). IGFBP-3 expression in liver tissue analysis showed that, differences between the three groups was statistically significant (P<0.05), pairwise comparisons, the control group was higher than mild and severe hypoxic group, there were significant differences (P<0.05), mild hypoxia and severe hypoxia group had no significant difference (P>0.05). Conclusion:IGF-1 and IGFBP-3 in the liver of mild hypoxia group, severe hypoxic group and control group showed that their transcription levels and the severity of hypoxia had no significant correlation.

A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial

Objective: To evaluate the effects of 20 weeks of resistance and concurrent training on psychotic and depressive symptoms, quality of life outcomes, and serum IGF-1, IGFBP-3, and brain-derived neurotrophic factor (BDNF) concentrations in patients with schizophrenia. Methods: In this blind, randomized controlled clinical trial, 34 patients with schizophrenia were assigned to one of three groups: control (CTRL, n=13), resistance exercise (RESEX, n=12), or concurrent exercise (CONCEX, n=9). Symptoms, quality of life, strength, and other variables were assessed. Results: A significant time-by-group interaction was found for the RESEX and CONCEX groups on the Positive and Negative Syndrome Scale (PANSS) total score for disease symptoms (p = 0.007), positive symptoms (p = 0.003), and on the arm extension one-repetition maximum (1RM) test (p = 0.016). In addition, significant improvements on negative symptoms (p = 0.027), on the role-physical domain of the Short Form-36 Health Survey (p = 0.019), and on the chest press 1RM test (p = 0.040) were observed in the RESEX group. No changes were observed for the other variables investigated. Conclusions: In this sample of patients with schizophrenia, 20 weeks of resistance or concurrent exercise program improved disease symptoms, strength, and quality of life. ClinicalTrials.gov: NCT01674543.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Effect of IGFBP-3 in the Inhibition of Gastric Carcinoma Cells Proliferation byResveratrol / 医药导报

Objective To study the expression of insulin like growth factor binding proteins 3 (IGFBP-3) during inhi-bition of resveratrol (Res) on cell proliferation. Methods The inhibitory effect of Res on BGC-823 cells was determined by MTT method; Real-time qRT-PCR and western blot were applied to detect the expression of IGFBP-3 in Res-treated BGC-823 cells. In addition, cytometry was used to determine the proliferation and apoptosis of Res-treated BGC-823 after knockdown of IG-FBP-3 by siRNA. Results Upon Res (20,40, 80 and 160 μmol · L-1 ) treatment,the viability of BGC-823 cells was (82. 35±10. 65)% ,(74. 30±12. 36)% ,(62. 80±14. 66)% and (50. 75±11. 14)% , respectively. The mRNA and protein ex-pression of IGFBP-3 elevated as high as 2. 96-fold compared to the control group (P<0. 05). The cell viability of BGC-823 cells with IGFBP-3 knockdown was significantly higher than that of the wild type ( P < 0. 05 ) only at high Res concentration (160 μmol·L-1 ). Meanwhile,IGFBP-3 knockdown led to a significant decrease on cell apoptotic rate by Res (160 μmol·L-1 ) [(20. 13±9. 12)% vs (35. 48±11. 12)% ,P<0. 05)]. Conclusion Res can inhibit BGC-823 cell proliferation and promote cell apoptosis, the underlying mechanism of which may be related to the overexpression of IGFBP-3 in BGC-823 cells.

Relationship between polymorphisms in IGF-1 and IGFBP-3 and non-smoking female lung cancer / 中国肿瘤临床

Objective:This study aimed to investigate the associations between single-nucleotide polymorphism (SNP) of IGF-1 and IGFBP-3 gene and risk of non-smoking female lung cancer in Chinese population. Methods:Genotyping was performed using the TaqMan method in 287 histologically confirmed non-smoking female lung cancer cases and 281 healthy controls. Results:The geno-type distributions of IGF-1 polymorphisms were significantly different between cases and controls (P3 cm. Conclusion:The IGF-1 polymorphism was associated with the risk of lung cancer and prognosis among non-smoking female. More rigorous laboratory studies of large sample population and functional studies are warrant-ed to confirm our findings.

The variation of IGF-1,IGFBP-3 in the development of rats’ non-alcoholic fatty liver disease / 中国比较医学杂志

Objective To observe the expression of insulin-like growth factor 1 (IGF-1),insulin-like growth factor binding protein 3 ( IGFBP-3) in rats’ serum with non-alcoholic fatty liver disease ( NAFLD) and the impact of Polyene phosphatidyl choline .Methods NAFLD model was induced by feeding the SD rats with a high-fat diet, with Polyene phosphatidyl choline to intervene .Observe the pathological changes of the rats ’ liver tissue dynamically after HE staining . Detect the contents of IGF-1,IGFBP-3 in serum dynamically through the immuno radio metric assay ( IRMA).Results There were no obvious exception of the liver tissue pathology in the normal group at each time .With the extension of a high-fat diet,the liver tissue of the model group increased on fatty change ,the degree of inflammation ,the balloon sample change , the NAFLD activity score at 4,8,12weeks.IGF-1,IGFBP-3 in serum were decreased significantly ,and the model set was significantly lower than the normal group at the same phase .After the application of polyene phosphatidyl choline ,the degree of rat liver tissue inflammation and the NAFLD activity score were reduced significantly when compared with model group , while the level of IGF-1,IGFBP-3were significantly higher .Conclusion The levels of IGF-1,IGFBP-3 in the rats’ serum reduce in the development of non-alcoholic fatty liver disease .

The effect of growth hormone in poor responders undergoing COH / 中国基层医药

Objective To observe the efficacy of growth hormone ( GH) co-treatment in poor responders undergoing IVF-ET.Methods To analyze all the ovaries low response patients treated by IVF/ICSI,80 cases were ran-domly divided into two groups:40 patients in GH group were given GH along with Gn daily until the HCG administra-tion.40 patients in the control group received the same treatment protocol except the GH co -treatment.The catching spawn number and MⅡova,fertile rate,the number of perfect embryos ,pregnant rate were observed .The serum con-centrations of IGF-I,IGFBP-3 were detected by ELISA and compared between the two groups .Results The number of oocytes retrieved ,number of MII oocytes ,cleavage ,number of embryos available of GH group were increased without statistical significance(all P>0.05 ).The serum IGFBP-3 level of 2 groups had no statistical significance .The fertile rate,pregnant rate ,serum IGF-I level were significantly higher in GH group than those in the control group ( all P<0.05).Conclusion GH co-treatment in poor responders could improve the outcome of IVF-ET,which imply that GH could improve the quality of oocytes and embryos related to the elevated IGF-1 level in serum .

Correlation of senile hip fracture type with expressions of insulin-like growth factor and its binding proteins / 中华创伤杂志

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.

Factores de crecimiento, variables antropométricas maternas y tamaño de recién nacidos de término / Insulin, cortisol, IGF, IGFBP-3 and maternal anthropometric variables in full term newborns

Introduction: Fetal growth is a physiological phenomenon involving maternal, placentary and fetal factors. Objective: To analyze growth factors and maternal anthropometric variables in full-term newborns (NB) and compare them to their size. Patients and Methods: 138 newborns, 37-41 gestational weeks, sorted according to size in low, normal and large for gestational age. Umbilical cord blood was measured for: ELISA, insulin, cortisol, IGF, IGFBP-3. Results: A statistically significant difference was seen between maternal weight at the beginning and end of pregnancy, and BMI (body mass index) at the beginning of pregnancy with the size of the NB (p < 0.001). There was no significant difference between growth factors and NB size. Conclusion: Insulin, Cortisol, IGF1, IGFBP-3 do not show statistically significant differences with the size of a newborn, although the mean value of growth factors in normal and large NB for gestational age, were twice than mean values in low for gestational age newborns. There is a positive, statistically significant correlation between the size of the newborn, and the size of the mother, weight at the beginning and end of the pregnancy and the Body Mass index of the mother at the beginning of the pregnancy.

Introducción: El crecimiento fetal es un fenómeno fisiológico complejo en el que intervienen factores maternos, placentarios y fetales. Objetivo: Analizar factores de crecimiento y variables antropométricas maternas en recién nacidos (RN) de término y compararlos con el tamaño de los RN. Pacientes y Método: Estudio prospectivo, descriptivo, transversal, que incluyó a 138 RN entre 37 y 41 semanas, clasificados según tamaño en PEG, AEG y GEG. En sangre de cordón se midió por ELISA, Insulina, cortisol, IGF-1 e IGFBP-3. Resultados: Hubo diferencia estadísticamente significativa (p < 0,01) entre: peso materno al inicio, peso materno al término e índice de masa corporal (IMC) al inicio de la gestación con el tamaño del RN. Hubo correlación positiva entre las variables antropométricas maternas y el peso del RN (p < 0,001). No hubo diferencia significativa entre los factores de crecimiento y el tamaño de los RN. Conclusión: Insulina, cortisol, IGF-1 e IGFBP-3 no muestran diferencias estadísticamente significativas según el tamaño de RN, aunque las medianas de los factores de crecimiento analizados en RN AEG y GEG duplican los valores de los RN PEG. Se observó correlación positiva y estadísticamente significativa entre el tamaño del RN y talla materna, peso al inicio de la gestación, peso al término de la gestación e IMC al inicio de la gestación.

Plasma levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in women with cervical neoplasia / 부인종양

OBJECTIVE: The goal of this study was to investigate the relationship between plasma levels of insulin-like growth factors-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) and the risk for cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: Plasma levels of IGF-1 and IGFBP-3 of 44 cervical cancer patients, 82 CIN patients and 40 neoplasm-free patients were investigated. Then the associations of the plasma levels of IGF-1 and IGFBP-3 with cervical neoplasm or its clinicopathologic parameters were analyzed. RESULTS: The mean IGF-1 concentrations were significantly different among the control, CIN, and cervical cancer groups; the levels were higher in the CIN group compared to the controls. According to the quartile category, the plasma IGF-1 level was significantly higher (p=0.0015) in the CIN group than in the controls. The IGFBP-3 level showed no association between the controls and CIN groups (p=0.842). Although the mean IGF-1/IGFBP-3 molar ratio had borderline significance (p=0.08) among the study population, the quartile comparison showed a significantly higher IGF-1/IGFBP-3 molar ratio in the CIN group compared to the control group (p=0.041). CONCLUSION: Plasma levels of IGF-1 and the IGF-1/IGFBP-3 molar ratio might be useful for the development early detection of cervical lesions and used as an adjuvant diagnostic tool for cervical neoplasia after more larger scale research.

Associations of IGF-I, IGFBP-3 on early Catch-up Growth in Small for Gestational Age Infants / 대한주산의학회잡지

OBJECTIVE: This study was aimed to analyze the effect of Insulin-like growth factor (IGF)-I and Insulin-like growth factor binding protein (IGFBP)-3 on early catch-up growth in small for gestational age (SGA) infants. METHODS: We prospectively studied in 18 SGA infants who were admitted at Chungnam National University Hospital from January 2004 to January 2006. We divided them into two groups of intrauterine growth retardation; symmetric and asymmetric type. Maternal and neonatal characteristics and the value of IGF-1 and IGFBP-3 at birth were compared between the two groups. After 12 months later, we checked their body weight and height to evaluate catch-up growth. RESULTS: Among 18 SGA infants, 5 were male and 13 were female. Average gestational age at birth was 38.4+/-1.1 weeks. Average birth weight was 2,359+/-154 g. Nine babies showed symmetric intrauterine growth retardation. Thirteen babies achieved catch-up growth at 12 month of age. There was no correlation between the characteristics of SGA and catch-up growth. However, the IGF-I and IGFBP-3 values were significantly higher in babies who showed catch-up growth. CONCLUSION: We were able to predict catch-up growth at early infancy by evaluating serum IGF-I and IGFBP-3 values at birth in SGA infants.

Correlation between the Expression Reduction of Insulin-like Growth Factor Binding Protein (IGFBP)-3 and PTEN and the Clinicopathological Parameters in Breast Cancer

PURPOSE: Insulin-like growth factor binding protein (IGFBP-3) and phosphatase and tensin homolog (PTEN) are tumor-suppressor genes that may be involved in breast tumorigenesis. However, the roles of these genes in the regulation of breast cancer growth or progress are unclear. In this study, we aimed to find any correlation between the reduction of IGFBP-3 or PTEN protein expression in cancer tissues and the clinicopathological parameters in breast cancer. METHODS: We collected both cancer and adjacent normal tissues from 46 breast cancer patients (from January 1 to December 31, 2006), and checked the IGFBP-3 and PTEN protein levels in cancer and adjacent normal tissues using Western immunoblot. We evaluated the correlation of reduction status of IGFBP-3 and PTEN protein expression with variable clinicopathological parameters. RESULTS: The frequency of IGFBP-3 and PTEN protein reduction in cancer tissue, compared to adjacent normal tissue, was 63.0% and 34.8%, respectively. And in 87.5% of patients, who showed significant PTEN reduction, IGFBP-3 protein expression was reduced in cancer tissues. In contrast, IGFBP-3 protein reduced in only 50% of patients who didn't show PTEN reduction. However, we did not find any significant correlation between reduction of IGFBP-3 or PTEN expression in cancer tissue and variable clinicopathological parameters. CONCLUSION: The IGFBP-3 and PTEN genes were expressed in all breast cancer tissues. Nonetheless, we did not find any significant relationship between reduction of IGFBP-3 or PTEN expression and the clinicopathological parameters in this study. Therefore, further studies are needed to document the roles of IGFBP-3 and PTEN genes in breast cancer growth or progress.

The role of insulin like growth factor (IGF)–1 and IGF-binding protein-3 in diagnosis of growth hormone deficiency in short stature children.

Objective. To evaluate the role of IGF-1 and IGFBP-3 in diagnosis of short stature children and adolescents in whom Growth Hormone Deficiency (GHD) was found. Methods. In this cross sectional study the referred short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in 2003-2005 were studied. The inclusion criteria were proved short stature based on the physical examination, weight, height, standard deviation score (SDS) of height < -2 , with considering stage of puberty and predicted height in children without any genetic or chronic disorders. The exclusion criteria were any positive physical or laboratory data suggesting hypothyroidism, rickets or liver disorders. For all patients a provocative growth hormone test was performed with propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as peak(cutoff ) serum GH level under 10 ìg/L and low IGF-1 and IGFBP-3 considered as cutoff serum level under -2 standard deviation. Results. Eighty one short stature patients (39 boys and 42 girls) with mean age of 10.6 ± 3.5 years completed the study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3. There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3 in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3, respectively. Conclusion. No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of these tests in assessment of GHD was poor.