乳腺癌患者血清胰岛素样生长因子-1及结合蛋白-3的变化及意义

目的探讨乳腺癌患者血清胰岛素样生长因子-1（IGF-1）、胰岛素样生长因子结合蛋白-3（IGFBP-3）和两者比率的变化及临床意义。方法80例良性乳腺肿瘤和135例乳腺癌患者术前采集空腹血分离血清-30℃冻存，用ELISA法测定标本的IGF-1和IFGBP-3浓度，用免疫组化法检测乳腺癌标本nm23基因。结果乳腺癌和良性乳腺肿瘤两组间IGF-1浓度和IGF-1：IFGBP-3呈高度显著差异（P〈0．01）．而IGFBP-3差异无显著意义（P〉0．05）。乳腺癌患者绝经前后IGF-1差异有显著意义（P=0．04），绝经前或有淋巴结转移的乳腺癌患者IGF-1：IGFBP-3明显高于绝经后或无淋巴结转移的乳腺癌患者。nm23阳性和阴性的乳腺癌之间血清IFGBP-3浓度差异有显著意义（P=0．01），但IGF-1浓度差异无显著意义。结论检测血清IGF-1、IGFBP-3有助于筛选和确定乳腺癌高危患者，从而有利于早期诊断及判断预后。     

早产儿胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3早期检测的临床意义

目的:研究早产儿早期胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)水平,指导围产期临床孕产妇及早产儿合理营养干预。方法:对145例早产儿生后3天内进行IGF-1I、GFBP-3测定,将其按小于胎龄儿与适于胎龄儿、小早产儿(小于34周)与晚期早产儿(大于34周)、双胞胎大体重与小体重3种方式对比分组,分别比较IGF-1I、GFBP-3水平。结果:145例早产儿生后3天内监测IGF-1I、GFBP-3值显示适于胎龄儿组明显高于小于胎适龄儿组,大于34周组明显高于小于34周组,大体重组明显高于小体重组,组间比较有极显著性差异(P<0.01)。结论:应加强围生期孕产妇管理,避免早产和胎儿宫内发育迟缓发生,早产儿、小于胎龄儿生后应尽早给予合理营养支持。     

小于胎龄儿胰岛素样生长因子-1、皮质醇及胰岛素水平与胎儿生长发育的相关性分析

目的分析胰岛素样生长因子-1（IGF-1）、皮质醇（Cor）、胰岛素水平与小于胎龄儿胎儿生长发育的相关性。方法 218例新生儿,按其出生体质量将其分为小于胎龄组（SGA）和适于胎龄儿组（AGA）比较小于胎龄儿组与适于胎龄儿组出生体质量、身长、头围以及胰岛素样生长因子-1、皮质醇、胰岛素水平的差异,并分析胰岛素样生长因子-1、皮质醇及胰岛素水平与胎儿生长发育的相关性。结果小于胎龄儿组IGF-1及胰岛素水平低于适于胎龄儿组,Cor高于适于胎龄儿组,其差异均具有统计学意义;IGF-1与新生儿出生体质量（r=0.71,P=0.000）、身长（r=0.65,P=0.000）及头围（r=0.63,P=0.000）均呈正相关,Cor与出生体质量相关系数临界检验水准（r=0.42,P=0.052）。结论 IGF-1、Cor与小于胎龄儿生长发育有关,可能对其生长发育起重要调节作用。     

DR患者血清中生长因子水平变化的研究

目的探讨2型糖尿病（T2DM）视网膜病变（DR）患者血清中胰岛素样生长因子-Ⅰ（IGF-Ⅰ）、IGF-Ⅱ和IGF结合蛋白-3（IGFBP-3）水平的变化及意义。方法用免疫放射分析法（IRMA）测定50例T2DM患者[包括14例无DR的T2DM患者（NDR）、16例单纯型DR患者（BDR）、20例增生型DR患者（PDR）]及22例正常对照者血清中IGF-Ⅰ、IGF-Ⅱ和IGFBP-3的水平。结果糖尿病组血清中IGF-Ⅰ水平显著高于正常对照组（P〈0．01），IGF-Ⅱ水平显著低于正常对照组（P〈0．01），两者呈显著负相关（r=0．305，P〈0、01）；PDR组IGF-Ⅰ水平显著高于BDR组（P〈0．01），后者又显著高于NDR组（P〈0．05）；PDR组和BDR组IGF-Ⅱ水平显著低于NDR组（P〈0．05）。NDR组、BDR组和PDR组间IGFBP-3水平无显著性差异（P〉0．05）。结论IGF-Ⅰ和IGF-Ⅱ可能参与了DR的病理过程，并与视网膜病变类型相关。     

宫内发育迟缓儿与胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3关系的研究

目的研究宫内发育迟缓（IUGR）儿与胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）的关系。方法用放射免疫法测定该院及复旦大学附属妇产科医院确诊的宫内发育迟缓儿（92例）和同期正常出生体重儿（AGA）（32例）脐血IGF-1和IGFBP-3的水平。结果IUGR组IGF-1为（29．2±26．5）μg／L，IGFBP-3为（1364．7±703．5）μg／L，对照组分别为（61．1±56．4）μg／L、（2344．7±1573．3）μg／L，两组比较差异有统计学意义。结论IGF-1和IGFBP-3对胎儿的生长发育起着重要的调节作用。     

生长素、瘦素及胰岛素样生长因子-1在小于胎龄儿生长追赶中的作用

目的探讨生长素（Ghrelin）、瘦素（Leptin）及胰岛素样生长因子-1（IGF-1）在小于胎龄儿（SGA）生长追赶（CUG）中的作用。方法选择50例足月适于胎龄儿（AGA）和50例SGA,随访3年,分析SGA的CUG情况,对比AGA组与SGA组,及AGA组与有CUG组和无CUG组体格发育指标及外周血指标。结果AGA组与SGA组新生儿体重、身长、头围、Ghrelin、IGF-1及Leptin差异有统计学意义（P〈0．05）。SGA组50例儿童中38例（76．00％）有CUG,12例（24．00％）无CUG。同龄AGA组、有CUG组、无CUG组WtSDS、HtSDS值差异有统计学意义（P〈0．01）,Ghrelin、IGF-1及Leptin水平差异有统计学意义（P〈0．01）。有CUG组外周血Ghrelin水平与WtSDS值、IGF-1、Leptin水平呈负相关,IGF-1、Leptin水平与WtSDS、HtSDS值呈正相关,IGF-1与Leptin水平呈正相关（P〈0．05）。结论出生后SGA存在高Ghrelin水平,低IGF-1、Leptin水平状态,有CUG的SGA3年后体格指标和Ghrelin、IGF-1、Leptin水平与AGA差异减小。SGA与Ghrelin抵抗、CH—IGF轴损害及胰岛素抵抗有关。     

重组人生长激素对小于胎龄儿血清胰岛素样生长因子1、胰岛素样生长因子结合蛋白3及身高均值标准差积分的影响

目的探讨血清胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）、两者比值及身高均值标准差积分（HtSDS）在重组人生长激素（rhGH）治疗小于胎龄儿（SGA）中的临床应用价值。方法对32例确诊为追赶生长失败的SGA患儿应用rhGH治疗（0．15～0．20u·b^-1·d^-1）,每晚睡前皮下注射,治疗3、6、9、12个月后进行随访,比较治疗前后的血清IGF-1、IGFBP-3,HtSDS、年生长速率（GV）的变化。结果GV治疗前为（4．1±0．5）cm／年,治疗后3、6、9、12个月分别升至（12．4±3．2）cm／年、（11．0±2．3）cm／年、（10．1±3．5）cm／年、（9．4±1．8）cm／年,显示治疗后追赶生长明显（F=51．35,P〈0．01）;HtSDS治疗前为（-2．81±0．64）,治疗后分别为（-2．55±0．73）、（-2．39±0．65）、（-2．21±0．58）和（-2．09±0．94）,显示治疗后身高与同年龄同性别正常儿童差距逐步缩小,与治疗前相比差异有统计学意义（F=4．99,P〈0．01）。IGF-1、IGFBP-3明显升高,各监测时间点和治疗前相比差异有统计学意义（F=34．52、14．04,均P〈0．01）,以IGF-1升高更明显,3个月之后维持在较高的水平,6个月达高峰;IGF-1／IGFBP-3比值和治疗前相比有所上升,但差异无统计学意义（F=1．82,P〉0．05）。rhGH治疗6个月内,血清IGF-1和身高标准差积分相对治疗前的变化（AHtSDS）存在显著正相关（r3=0．72,r6=0．91）,9个月后不存在相关性（r9=0．26,r12=0．33）。治疗期间未发生严重不良事件。结论rhGH治疗SGA后IGF-1、IGFBP-3升高,以IGF-1升高更明显,6个月内血清IGF-1和AHtSDS存在显著正相关,9个月后不存在相关。rhGH治疗小于胎龄儿是安全有效的。     

乳腺癌患者血清胰岛素样生长因子-1及结合蛋白-3含量测定

目的探讨胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)在乳腺癌中的表达和意义,并研究其与化疗疗效的关系。方法运用酶联免疫吸附法(ELISA)检测32例乳腺癌患者(A组),20例乳腺良性肿瘤患者(B组)和15例健康人(C组)血清中IGF-1和IGFBP-3的含量。结果 A组血清中IGF-1水平为(628.25±124.50)μg/L,B组血清中IGF-1水平为(435.46±116.86)μg/L,C组血清中IGF-1水平为(413.65±104.12)μg/L,A组明显高于B、C组且差异有统计学意义(P<0.05),但B组与C组之间差异无统计学意义(P>0.05)。A、B、C组血清中IGFBP3水平分别为(3596.12±1056.32)μg/L、(3856.12±1142.39)μg/L和(3912.65±1153.14)μg/L,3组之间差异无统计学意义(P>0.05)。15例化疗有效的患者,化疗2周期后IGF-1水平较化疗前明显降低,而IGFBP3水平呈高表达(P<0.05)。结论血清IGF-1和IGFBP-3含量变化有助于乳腺癌的辅助诊断和化疗疗效预测。     

子宫肌瘤患者血清胰岛素样生长因子结合蛋白3和胰岛素样生长因子的检测及意义

目的 研究胰岛素样生长因子结合蛋白3( IGFBP-3)和胰岛素样生长因子1(IGF-1)在子宫肌瘤血清中的表达及其相关性,探讨两者在子宫肌瘤发生发展中的作用.方法 采用ELISA法检测100例子宫肌瘤患者与50例健康妇女(对照组)血清IGFBP-3和IGF-1的含量.结果 子宫肌瘤分泌期与增殖期患者血清IGFBP-3浓度低于对照组(t=11.98,10.08,均P＜0.01),而IGF-1浓度显著高于对照组(t=11.22,8.97,均P＜0.01),而分泌期与增殖期血清IGFBP-3和IGF-1差异均无统计学意义(t=1.12,1.04,均P＞0.05);相关性结果表明,肌瘤个数与血清IGFBP-3浓度呈负相关(r=-0.476,P＜0.01),与IGF-1浓度正相关(r=0.527,P＜0.01);子宫肌瘤组IGFBP-3与IGF-1浓度在血清中表达强度呈正相关(r=-0.654,P＜0.01).结论 子宫肌瘤患者血清中IGFBP-3表达降低及IGF-1表达升高可能与子宫肌瘤的发生、发展有关.     

新生儿缺氧缺血性脑病血清胰岛素样生长因子-Ⅰ及胰岛素样生长因子结合蛋白-3水平分析

目的研究血清胰岛素样生长因子Ⅰ(IGF-Ⅰ)、胰岛素样生长因子蛋白-3(IGFBP-3)对新生儿缺氧缺血性脑病(HIE)的病情评估及预后判断的价值。方法采用酶联免疫吸附测定法检测60例不同程度HIE新生儿生后72h、28d血清IGF-I和IGFBP-3水平。选取同期、同龄30例健康新生儿为对照组,进行上述检测,并进行新生儿神经行为测定(NBNA)。结果①HIE组患儿急性期(生后72h)血清IGF-I和IGFBP-3水平下降,恢复期(生后28d)有所回升;上述两项指标水平均随病情加重而呈下降趋势。急性期各组间比较,差异均有统计学意义。恢复期:轻度组水平接近正常;血清IGF-Ⅰ水平中度组与轻度组、重度组比较,差异均有统计学意义;血清IGFBP-3水平中度组与轻度组比较,差异无统计学意义,与重度组比较,差异有统计学意义。结论 HIE患儿血清IGF-Ⅰ、IGFBP-3水平均下降,且病情越重,下降越明显,恢复期有所回升,但仍低于正常,提示IGF-1、IGFBP-3对临床评价HIE危重程度及预后有重要意义。     

Serum IGF-1 and IGFBP-3 levels in subclinical hypothyroid women

Thyroid status is known to influence growth in mammals. The aim of this study is to investigate the possible relationship between autoimmune subclinical hypothyroidism and growth hormone (GH), insulin-like growth factor-1(IGF-1) and insulin-like growth factor binding protein-3(IGFBP-3) levels. Thirty-five women with autoimmune subclinical hypothyroidism, 33 years of age, were used as controls and enrolled in the study. Free triiodothyronin (FT3), free thyroxin(FT4), thyrotropin(TSH), anti-thyroid peroxidase(Anti-TPO), anti-thyroglobuline(Anti-Tg), GH, IGF-1 and IGFBP-3 levels were measured in blood samples and correlations among these parameters were evaluated. We found no significant differences in GH, IGF-1 or IGFBP-3 between patients and controls. In patients and controls, there were no correlations among thyroid hormones and IGF-1 or IGFBP-3 levels, but GH levels were correlated with FT3, FT4 and TSH only in patients’ group. In controls, only IGF-1 and IGFBP-3 levels were correlated. The present study suggests that subclinical hypothyroidism with high TSH and antibody status does not affect IGF-1 and IGFBP-3 levels in adult women. To our knowledge, this is the first study concerning the relationship between autoimmune subclinical hypothyroidism and IGF-1 and IGFBP-3 levels.     

Effects of parenteral nutrition with and without GH on the GH/IGF-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis

Postoperative hepatic insulin-like growth factor-1 (IGF-1) production may be severely disturbed in patients with liver cirrhosis. Complex alterations in the GH/IGF-1 axis are thought to play an important role in the protein catabolism that complicates major surgical procedures. The aim of this study was to explore the effects of parenteral nutrition (PN) with and without growth hormone (GH) on the GH/IGF-1 axis after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis and evaluate the potential roles of recombinant human GH (rhGH) therapy. Twenty-four patients with HCC with cirrhosis who underwent hepatectomy were randomly divided into two groups: a PN group (n = 12) and an rhGH + PN group (n = 12). Liver function, serum GH, IGF-1 and IGFBP-3 were measured before the operation and at post-operative days (POD) 1 and 6. Insulin-like growth factor-1 and IGFBP-3 mRNA in the liver tissue was detected by RT-PCR. The liver Ki67 immunohistochemistry staining was studied. At the same time, 12 patients with cholelithiasis or liver hemangioma who underwent operation served as normal control group. On POD 6, serum prealbumin, GH, IGF-1, IGFBP-3, hepatic IGF-1 mRNA, IGFBP-3 mRNA and liver Ki67 LI were higher in the rhGH + PN group than in the PN group. There was no significant difference in the 6-and 12-month tumor-free survival rate and the median tumor-free survival time between the PN group and the rhGH + PN group (P>0.05). These data indicate that rhGH + PN could ameliorate the changes in the GH/IGF-1 axis after hepatectomy for HCC in the setting of cirrhosis.     

来曲唑辅助治疗生长激素缺乏型矮小症男童的临床价值

目的:探讨来曲唑在生长激素缺乏型矮小症男童的临床应用价值.方法:回顾性分析2016年3月至2018年6月安徽医科大学第二附属医院收治的80例生长激素缺乏型矮小症男童的临床资料,按治疗方案分为研究组和对照组各40例.对照组给予生长激素治疗,研究组在生长激素基础上加用来曲唑辅助治疗,均治疗2年,比较两组患儿治疗前、治疗1年...     

Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding

Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been implicated in the promotion and aggressiveness of breast, prostate, colorectal, and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them attractive candidates as therapeutics for cancer prevention and control. Recombinant human IGFBP-2 significantly attenuated IGF-1-stimulated MCF-7 cell proliferation with coaddition of 20 or 100 nM IGFBP-2 (50 or 80% inhibition, respectively). We previously identified IGF-1 contact sites both upstream and downstream of the CWCV motif (residues 247-250) in human IGFBP-2 (J Biol Chem 276:2880-2889, 2001). To further test their contributions to IGFBP-2 function, the single tryptophan in human IGFBP-2, Trp-248, was selectively cleaved with 2-(2'nitrophenylsulfenyl)-3-methyl-3 bromoindolenine (BNPS-skatole) and the BNPS-skatole products IGFBP-2(1-248) and IGFBP-2(249-289) as well as IGFBP-2(1-190) were expressed as glutathione S-transferase-fusion proteins and purified. Based on competition binding analysis, deletion of residues 249 to 289 caused an approximately 20-fold decrease in IGF-1 binding affinity (IGFBP-2 EC50 = 0.35 nM and IGFBP-2(1-248) = 7 nM). Removal of the remainder of the C-terminal domain had no further effect on affinity (IGFBP-2(1-190) EC50 = 9.2 nM). In kinetic assays, IGFBP-2(1-248) and IGFBP-2(1-190) exhibited more rapid association and dissociation rates than full-length IGFBP-2. These results confirm that regions upstream and downstream of the CWCV motif participate in IGF-1 binding. They further support the development of full-length IGFBP-2 as a cancer therapeutic.     

Glucocorticoid receptor function suppresses insulin-like growth factor 1 activity in human KLE endometrial-like cells

We analysed the glucocorticoid receptor (GR) regulation on the expression of insulin-like growth factor 1 (IGF-1), type I IGF receptor (IGF-1.R), IGF-binding protein 3 (IGFBP-3), urokinase-type plasminogen activator (uPA) and uPA receptor (uPA.R) mRNA in human KLE endometrial-like cells. We documented that KLE cells express IGF-1, IGF-1.R, uPA and IGFBP-3 mRNA, however not uPA.R mRNA. Exogenous administration of dexamethasone inhibited the proliferation of KLE cells without inducing apoptosis. The inhibition of dexamethasone on KLE cell proliferation was neutralized by exogenous administration of IGF-1. Furthermore, dexamethasone suppressed the expression of IGF-1 mRNA and IGF-1.R mRNA as well as the IGF-1 bioavailability in KLE cell culture media, but it did not alter the expression of uPA mRNA and IGFBP-3 mRNA in KLE cells. Since the peritoneal fluid of women with endometriosis is known to contain IGF-1, which stimulates the proliferation and inhibits the apoptosis of endometrial-like cells, it is conceivable that GR-mediated down-regulation of IGF-1 bioavailability may be of clinical relevance for endometriosis.     

重组生长激素改善肾病综合征患者低蛋白血症的研究

目的观察基因重组生长激素(recombinanthumangrowthhormone,rhGH)对肾病综合征(nephro-ticsyndrom,NS)患者血清总蛋白、白蛋白、胰岛素样生长因子-1(insulin-likegrowthfactor-1,IGF-1)和胰岛素样生长因子结合蛋白-3(insulin-likegrowthfactorbindingprotein-3,IGFBP-3)的作用。方法原发性NS患者100例,随机分为2组,治疗组50例,在常规治疗的基础上加用rhGH治疗;对照组50例用常规治疗。以放射免疫法测血清IGF-1及IGFBP-3水平,S-丽春红测24h尿蛋白定量,全自动生化仪检测血清蛋白。结果①rhGH治疗2周后血清IGF-1、IGFBP-3和血清蛋白与对照组相比显著上升;②rhGH治疗组与NS对照组相比尿蛋白排出差异无统计学意义。结论短期小剂量使用外源性rhGH能在不增加尿蛋白排出的情况下提高NS患者血清蛋白水平,且安全可靠。     

Use of ACE inhibitors is associated with elevated levels of IGFBP-3 among hypertensive older adults: results from the IlSIRENTE study

Objective Several studies in vitro or in rodent models have suggested a potential relationship between angiotensin-converting enzyme (ACE) inhibition and the insulin-like growth factor 1 (IGF-1) axis. However, this relationship has only rarely been investigated in humans. The aim of the present cross-sectional study was to assess the association of ACE inhibitors with free IGF-1 and IGFBP-3 in the blood of older hypertensive adults. Methods Data are from the baseline evaluation of the ilSIRENTE study, which enrolled 364 subjects aged 80 or older. For the present study we selected a subpopulation of 264 hypertensive participants without congestive heart failure. Free IGF-1 and IGFBP-3 in the blood were measured by a radioimmunoassay method. Analyses of covariance were performed to evaluate the differences in free IGF-1 and IGFBP-3 levels according to the use of ACE inhibitors. Results The mean age of participants was 85.7 years (SD: 4.9), 170 (64%) were women and 123 (47%) were using an ACE inhibitor. Following adjustment for potential confounders, the concentration of free IGF-1 was slightly, but not significantly higher among ACE inhibitor users than among non-users (0.74 vs. 0.65 ng/mL; p = 0.20). In contrast, ACE inhibitor users had a significantly higher IGFBP-3 serum levels than non-users (4821 vs. 4330 ng/mL; p = 0.005). In addition, the concentration of IGFBP-3 was significantly higher among ACE inhibitors users than among non-users of antihypertensive drugs (p = 0.02) and users of other antihypertensive drugs (p = 0.01). Conclusion Among hypertensive older adults, ACE inhibitors use is associated with higher IGFBP-3 levels.