Analysis Of Insulin-like Growth Factor Research Articles

Expression analysis of insulin-like growth factor 1, neutrophil/lymphocyte ratio, and inflammatory factors in children with Mycoplasmal pneumonia

Mycoplasma pneumonia (MPP) belongs to atypical pneumonia, which is caused by Mycoplasma pneumonia infection, accounting for 10–40% of children’s community pneumonia. It is more common in children at preschool age. The clinical symptoms of MPP are varied and difficult to cure. The research analyze the expression of inflammatory factors in MPP, neutrophil/lymphocyte ratio (NLR), insulin-like growth factor 1 (IGF1). The aim is to provide relevant basis for treatment and diagnosis of the disease. 40 normal children were selected as the control group. 78 children with MPP were selected as the observation group. The levels of interleukin-6 (IL-6) and interleukin-2 (IL-2) in peripheral blood were detected. Platelet/lymphocyte ratio (PLR) and NLR were tested. IGF1 expression was determined by ELISA. The correlation between IGF1, IL-6, IL-2NLR, PLR and the severity of MPP was analyzed. IL-2, NLR, and PLR significantly increased. The IGF1 in MPP group was lower than control group (P <0.05). IL-6 level in two group was no significant change. NLR, PLR and IL-2 were negatively correlated with IGF1. NLR, IL-2, PLR were positively correlated with MPP severity (P <0.05). NLR, PLR, and IL-2 were upregulated, whereas IGF1 was declined in MPP, which can be used to evaluate the progression of MPP.

PCR-RFLP Analysis of Insulin-Like Growth Factor 2 Gene Polymorphisms in Two Commercial Broiler Chicken Strains (Cobb 500 and Hubbard F-15) and Their Associations with Performance Traits.

The present research aimed to study the polymorphisms of the chicken insulin-like growth factor 2 (IGF2) in two commercial broiler breeds (Cobb 500 and Hubbard F-15). In total, 300 avian blood samples were obtained. The genomic DNA was isolated using a fast salt-extraction technique. Moreover, polymerase chain reaction (PCR) was used to amplify 1146 bp fragments of the gene. The amplified fragments were subjected to restriction enzyme digestion using the HinfI endonuclease enzyme, and the digested products were separated on a 2% agarose gel. The findings indicated that there were two alleles T and C for the target locus, with frequencies of 73.3% and 26.7%, respectively. Three distinct genotype variations, TT, TC, and CC, were found, with genotype frequencies of 59.1%, 28.4%, and 12.5%, respectively. A test based on actual and anticipated frequencies of various genotypic variances of the IGF2 gene revealed that the divergence from Hardy-Weinberg equilibrium was not significant (P≤0.01) in commercial broiler breeds (Cobb 500 and Hubbard F-15) chickens. In addition, it was found that birds with genotype TC had a greater body mass at 8 weeks of age, compared to those with genotypes TT and CC. It was determined that the IGF2 gene exhibited a significant degree of variability and might be regarded as a possible genetic marker in selection and breeding programs for poultry.

382 The Role of the IL-6-IGF-II Axis in Systemic Sclerosis-Associated Lung Fibrosis

OBJECTIVES/GOALS: Interleukin (IL)-6 is produced in excess in Systemic Sclerosis (SSc). Likewise, microarray analysis of Insulin-like Growth Factor (IGF)-II-treated NL fibroblasts revealed increased expression of the basic helix-loop-helix transcription factor, BHLHB2. Our goal is to delineate the role of BHLHB2 in the fibrotic response to IGF-II and IL-6. METHODS/STUDY POPULATION: Primary lung fibroblasts were cultured from human lung tissues at 37oC and 5% CO2. Cell cultures were stimulated with IL-6. Gene expression was measured using quantitative PCR (qPCR). IGF-II mRNA expression levels after IL-6 stimulation were compared with those of the housekeeping gene PPIB (Peptidylprolyl Isomerase B). Western blot was performed on nuclear and chromatin-bound subcellular fractions from treated lung fibroblasts. BHLHB2 protein levels were assayed in response to IGF-II in comparison to PBS as vehicle control. RESULTS/ANTICIPATED RESULTS: Results: Our results show that IL-6 increases IGF-II levels in fibroblasts. In turn, IGF-II increases BHLHB2 nuclear localization. We further show that IL-6 increases BHLHB2 levels and its nuclear localization in lung fibroblasts. Our findings are novel since the role of the transcription factor BHLHB2 in the IL-6 induced/ IGF-II-mediated fibrotic response in SSc lung disease remains unexplored. DISCUSSION/SIGNIFICANCE: Our findings may provide a rationale for combination therapy to block IL-6 and IGF-II function concomitantly and thus halt the progression of SSc pulmonary fibrosis (PF). Our findings may have wide implications for lung fibrosis associated with various diseases, since SSc-PF, is characterized by the activation of common fibrotic pathways.

Impact of the Choice of IGF-I Assay and Normative Dataset on the Diagnosis and Treatment of Growth Hormone Deficiency in Children

Background: The analysis of insulin-like growth factor I (IGF-I) is an important tool for pediatricians in the diagnosis and treatment of growth hormone deficiency in children. However, significant differences exist in IGF-I assays and normative datasets, which can have important clinical consequences. Methods: IGF-I analyses were performed using the IDS-iSYS platform on 1,897 samples from pediatric patients (0.5–18 years old). Z-scores were calculated based on normative IGF-I data from Bidlingmaier et al. (SD-BM) [J Clin Endocrinol Metab. 2014 May; 99(5): 1712–21] and normative IGF-I data from the IGF-I harmonization program in the Netherlands (SD-NL). The differences in Z-scores were analyzed at relevant clinical decision points (–2 SD, +2 SD). These normative datasets were also compared to normative data reported by Elmlinger et al. [Clin Chem Lab Med. 2004; 42(6): 654–64]. Results: The difference in Z-score between SD-BM and SD-NL was highest in males between 0 and 3 years old, exceeding 2 SD. Clinically relevant discordance between both Z-scores at –2 and +2 SD was found in 12.7% of all samples. The IGF-I levels at –2 and +2 SD reported in the normative dataset of Elmlinger et al. were up to 100% higher than the IGF-I levels reported by Bidlingmaier et al. or the Dutch harmonization program. Conclusion: Pediatricians and laboratory specialists should be aware of relevant differences that can exist between IGF-I assays and normative data. Well-defined pediatric reference ranges for the IDS-iSYS platform are highly desirable.

Circulating microRNA-99 family as liquid biopsy marker in pancreatic adenocarcinoma.

Recently, we identified the microRNA-99 family as unfavorable prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate its value as circulating biomarker for PDAC. Tissue and corresponding preoperative blood samples of 181 patients with PDAC UICC Stages I-IV (n = 90), intraductal papillary mucinous neoplasm (IPMN, n = 11), chronic pancreatitis (n = 40), pancreatic cystadenoma (n = 20), and age-matched healthy blood serum controls (n = 20) were collected between 2014 and 2017 prospectively. Expression of microRNA-21 as confirmatory marker and the microRNA-99 family, consisting of microRNA-99a, -99b, and -100, was analyzed by qRT-PCR. Target analysis of insulin-like growth factor 1 receptor (IGF1R) was performed using tissue array immunohistochemistry and Western blotting. Expression of microRNA-99 family members was significantly increased in macrodissected tumor tissue and corresponding blood serum samples (p < 0.05) of patients with PDAC of all stages. Correspondingly, its target protein IGF1R was upregulated (p < 0.001) in carcinoma tissue. Circulating and tissue-related microRNA-100 could well discriminate PDAC from healthy samples with area under the receiver operating characteristic (ROC) curve (AUC) values of 0.81 and 0.85, respectively. Low expression of circulating microRNA-100 was associated with significantly improved overall survival (p = 0.004) and recurrence-free survival (p = 0.03) in multivariate analyses. Circulating microRNA-21 was overexpressed in PDAC with fair discrimination between PDAC and healthy controls (AUC = 0.71) and decreased overall survival (p = 0.046) and recurrence-free survival (p = 0.03) in PDAC patients. Multivariate survival and ROC analyses identified circulating microRNA-100 as potential diagnostic and prognostic marker in PDAC patients.

Analysis of Insulin-Like Growth Factor I and Its Receptor of an Indian Major Carp Labeo rohita: An In silico Approach

Analysis of Insulin-Like Growth Factor I and Its Receptor of an Indian Major Carp Labeo rohita: An In silico Approach

IGFBP-2 and -3 co-ordinately regulate IGF1 induced matrix mineralisation of differentiating human dental pulp cells

Human dental pulp cells (DPCs), which are known to contain a subset of stem cells capable of reforming a dentin and pulp-like complex upon in vivo transplantation, were isolated from third molars of three healthy donors and differentiated to a matrix mineralisation phenotype using by culture in dexamethasone and l-ascorbic acid. qRT-PCR analysis of insulin-like growth factor ( IGF) axis gene expression indicated that all genes, except insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein-1 ( IGFBP-1), were expressed in DPCs. During differentiation upregulation of insulin-like growth factor binding protein-2 (IGFBP-2) and downregulation of insulin-like growth factor binding protein-3 (IGFBP-3) expression was observed. Changes in IGFBP-2 and IGFBP-3 mRNA expression were confirmed at the protein level by ELISA of DPC conditioned medium functional analysis indicated that IGF1 stimulated the differentiation of DPCs and that the activity of the growth factor was enhanced by pre-complexation with IGFBP-2 but inhibited by pre-complexation with IGFBP-3. Therefore changes in IGFBP-2 and -3 expression during differentiation form part of a co-ordinated functional response to enhance the pro-differentiative action of IGF1 and represent a novel mechanism for the regulation of DPC differentiation.

Immunohistochemical analysis of insulin-like growth factor 1 and its receptor in sporadic schwannoma/peripheral nerve sheath tumour.

ObjectiveTo investigate the immunohistochemical localization of insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) in archival specimens of sporadic schwannoma.MethodThis study retrospectively analysed the immunolocalization of IGF-1 and IGF-1R in schwannoma specimens collected from all patients with sporadic schwannoma that were treated by two institutions in Japan. The study also evaluated the association between the extent of the IGF-1 and IGF-1R immunoreactivity and several clinicopathological characteristics (age, sex and maximum tumour dimension).ResultsThe study examined a total of 29 sporadic schwannoma specimens. IGF-1 and IGF-1R immunoreactivity was detected in the majority of the specimens regardless of their anatomical location. IGF-1 and IGF-1R were not co-localized. There was no association between the extent of the IGF-1 and IGF-1R immunoreactivity and the clinicopathological characteristics of the patients.ConclusionsAs IGF-1 and IGF-1R immunoreactivity was detected in the majority of sporadic schwannoma specimens regardless of their anatomical location, these findings suggest that an IGF-1/IGF-1R loop could play a role in the tumorigenesis and progression of schwannomas via an autocrine–paracrine mechanism.

Quantitative analysis of insulin-like growth factor 2 receptor and insulin-like growth factor binding proteins to identify control mechanisms for insulin-like growth factor 1 receptor phosphorylation.

BackgroundThe insulin-like growth factor (IGF) system impacts cellular development by regulating proliferation, differentiation, and apoptosis, and is an attractive therapeutic target in cancer. The IGF system is complex, with two ligands (IGF1, IGF2), two receptors (IGF1R, IGF2R), and at least six high affinity IGF-binding proteins (IGFBPs) that regulate IGF ligand bioavailability. While the individual components of the IGF system are well studied, the question of how these different components integrate as a system to regulate cell behavior is less clear.ResultsTo analyze the relative importance of different mechanisms that control IGF network activity, we developed a mass-action kinetic model incorporating cell surface binding, phosphorylation, and intracellular trafficking events. The model was calibrated and validated using experimental data collected from OVCAR5, an immortalized ovarian cancer cell line. We then performed model analysis to examine the ability of IGF2R or IGFBPs to counteract phosphorylation of IGF1R, a critical step for IGF network activation. This analysis suggested that IGF2R levels would need to be 320-fold greater than IGF1R in order to decrease pIGF1R by 25 %, while IGFBP levels would need to be 390-fold greater. Analysis of The Cancer Genome Atlas (TCGA) data set suggested that this level of overexpression is unlikely for IGF2R in ovarian, breast, and colon cancer. In contrast, IGFBPs can likely reach these levels, suggesting that IGFBPs are the more critical regulator of IGF1R network activity. Levels of phosphorylated IGF1R were insensitive to changes in parameters regulating the IGF2R arm of the network.ConclusionsUsing a mass-action kinetic model, we determined that IGF2R plays a minor role in regulating the activity of IGF1R under a variety of conditions and that due to their high expression levels, IGFBPs are the dominant mechanism to regulating IGF network activation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0263-6) contains supplementary material, which is available to authorized users.

BRCA-mutated Invasive Breast Carcinomas: Immunohistochemical Analysis of Insulin-like Growth Factor II mRNA-binding Protein (IMP3), Cytokeratin 8/18, and Cytokeratin 14.

To evaluate the expression of insulin-like growth factor II mRNA-binding protein (IMP3), CK8/18, and CK14 in BRCA mutated and sporadic invasive breast carcinoma. Immunohistochemistry for IMP3, CK8/18, and CK14 was performed on 39 cases of invasive breast carcinomas with BRCA mutation (24 BRCA1, 14 BRCA2, and 1 dual BRCA1/BRCA2) and 54 cases of sporadic invasive breast carcinomas. The relationship between the IMP3, CK8/18, and CK14 and the tumor grade and molecular phenotypes were analyzed. IMP3, CK8/18, and CK14 positivity were present in 20 (51%), 22 (56%), and 14 (36%) of 39 BRCA-mutated breast carcinomas, and 11 (20%), 53 (98%), and 24 (44%) of 54 sporadic breast carcinomas respectively. The rates of IMP3 expression and absence of CK8/18 (44% versus 2%) in BRCA-mutated breast carcinomas was significantly higher than the sporadic breast carcinomas (p = 0.002 and p < 0.001). No significant difference was observed for CK14 among the two groups (p = 0.408). No significant difference was observed among BRCA1-related and BRCA2-related breast carcinomas in the immunoprofile for IMP3, CK8/18, and CK14. No significant correlation was identified between the expression of IMP3 and CK8/18 and the tumor grade in both BRCA-mutated and sporadic breast carcinomas (p > 0.05). In cases with luminal A and B phenotypes, the rates of expression of IMP3 and loss of CK8/18 were significantly higher in BRCA-mutated as compared to sporadic breast carcinoma (p < 0.001). In cases with basal-like phenotype, the absence of CK8/18 expression was significantly higher in BRCA-mutated breast carcinomas (54% versus 0%, p = 0.001), while no difference was observed for IMP3 expression (p = 0.435). Regardless of mutation type, histologic grade, or molecular phenotype, the absence of CK8/18 expression and presence of IMP3 expression are seen at much higher rate in BRCA mutated breast carcinomas.

Missense mutations in exon 2 of the MED12 gene are involved in IGF-2 overexpression in uterine leiomyoma.

Uterine leiomyoma (UL), the most common benign tumour found in females, is associated with many recurrent genetic aberrations, such as translocations, interstitial deletions and specific germline mutations. Among these, mutations affecting exon 2 of the mediator complex subunit 12 (MED12) gene are commonly detected in the majority of ULs. Mutational analysis of the MED12 gene, performed on 36 UL samples, revealed that 12 leiomyomas (33.4%) exhibited heterozygous missense mutations in codon 44 of exon 2 of the MED12 gene, four leiomyomas (11.1%) showed internal in-frame deletions, and two leiomyomas (5.5%) exhibited deletions involving intron 1-exon 2 junction, which caused a predicted loss of the splice acceptor. No mutations were detected in uterine myometrium (UM) and pseudocapsule (PC) samples, including those from women with a MED12 mutation in UL. These data showed that the PC is a healthy tissue that surrounds the UL to maintain UM integrity. Analysis of insulin-like growth factor 2 (IGF-2) and collagen type IV alpha 2 (COL4A2) mRNA expression levels in the same set of ULs revealed that only those with MED12 missense mutations expressed significantly higher levels of IGF-2 mRNA. In contrast, MED12 gene status does not appear to affect mRNA expression levels of the COL4A2 gene. On the basis of this finding, we suggest that the MED12 status stratifies the ULs into two mutually exclusive pathways of leiomyoma genesis, one with IGF-2 overexpression and the other with no IGF-2 activation. The occurrence of IGF-2 overexpression could be therapeutically targeted for the non-surgical treatment of leiomyomas.

A novel mass spectrometry‐based method for determining insulin‐like growth factor 1: assessment in a cohort of subjects with newly diagnosed acromegaly

To develop an alternative method to immunoassay for the quantitative analysis of insulin-like growth factor 1 (IGF-1) using a mass spectrometry (MS)-based approach. A stable isotope dilution Ultra High Performance Liquid Chromatography tandem MS (uHPLC-MS/MS)-based method for the quantification of IGF-1 was developed. The method employed Selected Reaction Monitoring (SRM) of two tryptic peptides derived from IGF-1, and utilised solid phase extraction for enrichment of the peptide fraction containing IGF-1 rather than immunocapture, so was less susceptible to assay interference. Plasma samples from 25 consecutive unselected patients with newly diagnosed acromegaly, collected both before and after 24 weeks of primary medical therapy with Lanreotide Autogel(®), were analysed by a widely used commercial immunoassay (Siemens Immulite 2000(®)) and by uHPLC-MS/MS. The uHPLC-MS/MS method showed good correlation with the immunoassay over a wide range of IGF-1 concentrations. The Passing and Bablock regression was: uHPLC-MS/MS (nmol/l) = 1.37 (95% confidence interval: 1.26-1.46) × immunoassay (nmol/l) + 3.14 (95% confidence interval: -2.71 to 10.32). Six patients had discordant growth hormone (GH) and IGF-1 levels following primary medical therapy, and in all six the immunoassay and uHPLC-MS/MS platforms returned comparable results. The method was not affected by concentrations of IGFBP3 up to 12,500 ng/ml. uHPLC-MS/MS offers an independent method for determining/validating IGF-1 in subjects with acromegaly. Further studies, including the establishment of age- and sex-matched reference ranges and calibration to the new International IGF-1 standard IS 02/254, are now required to allow its introduction in to routine clinical use.

Serum insulin-like growth factor-I adult reference values for an automated chemiluminescence immunoassay system

Analysis of insulin-like growth factor I (IGF-I) in serum is fundamental in order to aid in the diagnosis of growth hormone (GH)-related disorders, as well as in the diagnosis and follow-up of other diseases. Considering the importance of IGF-I local normal range, the aim of this study was to determine reference values for IGF-I (Immulite 2000) in a Brazilian adult population from the city of Rio de Janeiro. This study included samples of blood taken from 484 healthy subjects (251 men, 233 women) aged 18 to 70. The subjects agreed with this study, approved by the ethical committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil. The samples were analyzed by an automated immunochemiluminometric assay (ICMA). For data analysis, age and sex-specific figures were fitted after transformation of IGF-I values. In adulthood, a slow age-dependent decrease was seen. IGF-I in women were significantly higher than in men.The present study established age- and sexspecific IGF-I reference values, for the healthy Brazilian adult populatoin from the city of Rio de Janeiro, determined with the currently most widely IGF-I assay used in Brazil (Immulite 2000). Key words : Insulin-like growth factor I, chemiluminescence assay, reference range.

Molecular cloning, expression analysis of insulin-like growth factor I (IGF-I) gene and IGF-I serum concentration in female and male Tongue sole (Cynoglossus semilaevis)

Insulin-like growth factor I (IGF-I) is a polypeptide hormone that regulates growth during all stages of development in vertebrates. To examine the mechanisms of the sexual growth dimorphism in the Tongue sole (Cynoglossus semilaevis), molecular cloning, expression analysis of IGF-I gene and IGF-I serum concentration analysis were performed. As a result, the IGF-I cDNA sequence is 911 bp, which contains an open reading frame (ORF) of 564 bp encoding a protein of 187 amino acids. The sex-specific tissue expression was analyzed by using 14 tissues from females, normal males and extra-large male adults. The IGF-I mRNA was predominantly expressed in liver, and the IGF-I expression levels in females and extra-large males were 1.9 and 10.2 times as much as those in normal males, respectively. Sex differences in IGF-I mRNA expressions at early life stages were also examined by using a full-sib family of C. semilaevis, and the IGF-I mRNA was detected at all of the 27 sampling points from 10 to 410 days old. An increase in IGF-I mRNA was detected after 190 day old fish. The significantly higher levels of IGF-I mRNA in females were observed after 190 days old in comparison with males (P<0.01). The IGF-I concentrations in serum of mature individuals were detected by ELISA. The IGF-I level in the serum of females was approximately two times as much as that of males. Consequently, IGF-I may play an important role in the endocrine regulation of the sexually dimorphic growth of C. semilaevis.

Expression of GH/IGF-1 Axis Compounds in Moderate-Severe Crohn's Disease: Role of Mucosal Inflammation and Anti TNF-α Treatment

AIM: Growth failure in children and adolescents, weight loss and catabolism in adults, are well known features of active Crohn's disease (CD). Increasing evidence shows that these features may be due to growth hormone (GH) resistance caused by persistent chronic inflammation. Aim of this study was to evaluate, in CD patients, a possible peripheral GHresistance (intestinal mucosa), and eventual modifications following anti TNF-α treatment. MATERIALS AND METHODS: 9 patients (5 F, median age 42.2 years, range 19-67) with moderate-severe active CD (CDAI>220), consecutively scheduled to receive three infliximab infusions at a dose of 5 mg/kg for induction of remission, were studied. Biopsy specimens from normal appearing duodenal mucosa were collected, in the 2 weeks prior to the first and after the third infusion. Confocal and real time PCR analysis of insulin-like growth factor 1 (IGF-1), activated signal transducer and activator of transcription protein 5 (phosphoSTAT5) and suppressor of cytokine signalling protein 3 (SOCS-3) were carried out and normalised to GAP, 18S and H3 referring genes. Four dyspeptic patients (2 F, median age 39 years, range 24-57), who underwent upper endoscopy with duodenal biopsy sampling, represented our control group. Differences between CD patients and controls were analysed by one-way ANOVA and REST-coupled ANOVA analysis. RESULTS: In CD patients, a significant inverse correlation was found when comparing phospho-STAT5 levels with CDAI (r=-0.71; p=0.003). Confocal analysis showed a significant decrease in phospho-STAT5 immunoreactivity in sections from CD patients, compared to controls (p<0.001). After treatment, phospho-STAT5 levels significantly increased (p<0.001). Molecular data for phospho-STAT5 were in keeping with biochemical findings. At baseline, compared with controls, in CD patients, the PCR analysis of IGF-1, showed a trend towards a decrease, while SOCS3 showed a trend towards an increase. Following treatment, SOCS-3 and IGF-1 target genes showed a trend toward a decrease and an increase, respectively. Nevertheless, following infliximab induction treatment, IGF-1, phospho-STAT5 and SOCS-3 levels did not reach those of the control group. CONCLUSION: The present study underline the effect of inflammation on the growth hormone axis not only at the level of hepatic metabolism, but also in the intestinal mucosa, since biologic agents able to inhibit pro-inflammatory cytokines, in particular TNF-α, the main inflammatory mediator, reverse growth hormone resistance. These therapeutic approaches could prevent the onset of those clinical conditions with a negative impact on child growth and quality of life of adults.

Comparative Analysis of Insulin-like Growth Factor I and Tumour-associated Antigens in Cancer Patients at the Time of Diagnosis

Comparative Analysis of Insulin-like Growth Factor I and Tumour-associated Antigens in Cancer Patients at the Time of Diagnosis Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone with structure similar to insulin. Many experimental data support the suggestion that risk of cancer is higher among persons with raised concentration of IGF-1 and some studies support the role of IGF-1 as a biomarker of increased risk of development of colorectal (CRC) and breast cancer (BC). We have determined IGF-1, CA19-9, CEA, CA72-4 for colorectal, CA15-3 and CEA for breast cancer to clarify utility of IGF-1 as a biomarker of cancer presence at the time of diagnosis. In total, 42 men and 52 women with CRC and 139 women with BC were examined. The cut-off level for IGF-1 concentration in serum was established from results of apparently healthy 27 men and 130 women. An IGF-1 and tumour-associated antigens were detected by chemiluminescence's method using analyser Immulite 2000 (Siemens). Elevated level of IGF-1 was detected in 42.8% of men and 30.7% of women with colorectal cancer. The highest detection rates for CRC using a two biomarker combination were for men as well as for women (57.1% and 57.6%). IGF-1 showed higher detection rates between women with breast cancer in postmenopause vs. women at premenopausal age (33.6% vs. 27.7%). IGF-1 can be used as an additional biomarker for selected colorectal and breast cancer patient groups.

Serum Insulin-Like Growth Factor I Reference Values for an Automated Chemiluminescence Immunoassay System: Results from a Multicenter Study

Background: Analysis of insulin-like growth factor I in serum (S-IGF-I) is an integral component in the diagnosis of GH-related disorders and is going to be of interest in the diagnosis and follow-up of many disorders. The objective of the present study was to develop cross-sectional reference values for S-IGF-I measured by an automated chemiluminescence immunoassay (Nichols Advantage^®). Methods: The study included samples from 3,961 healthy subjects (2,201 males, 1,760 females) aged 1 month to 88 years. Six laboratories were involved in this study and the samples were analyzed by one of seven automated immunoassay systems run in these laboratories. For data analysis, polynomial age and sex-specific models were fitted after transformation of S-IGF-I values. Results: The results show the well-known age dependency of S-IGF-I levels. At ages <20, higher S-IGF-I levels were seen in girls with an estimated mean peak of 410 µg/l at age 14 and an estimated mean peak of 382 µg/l at age 16 in boys. Thereafter, a rapid decrease was seen to approximately 25 years of age, followed by a slow age-dependent decrease. In adulthood, S-IGF-I in males were slightly, but significantly higher than in females. It could be shown that the mean values of some reference sample subgroups differed significantly from the total mean. However, the multicenter approach used in this study reduces the impact of systematic population, sample handling and laboratory differences on the calculated reference mean. Conclusion: The present study establishes age- and sex-specific reference values for a fully automated immunoassay system based on a large population of healthy subjects. The established reference values may be used for this immunoassay system in different laboratories provided that the systematic difference between systems is low.

Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia.

Pre-eclampsia (PE) is uniquely a disease of pregnancy and is the major cause of foetal and maternal morbidity and mortality. Epidemiological studies show that PE is highly heritable, with a high incidence in all populations. The underlying pathology indicates that absent or shallow invasion of foetal trophoblasts into maternal arteries is a feature of true PE. The objective of this study was to determine the genetic factors influencing PE. A large number of mother-father-baby trios were collected in which the first pregnancy was complicated by severe PE. After careful examination of the epidemiology and pathology of the disease, two plausible candidate genes, namely insulin-like growth factor II (IGF-II) and HLA-G, were analysed for association with PE. No association was found between a commonly occurring polymorphism in IGF-II and PE. Three polymorphisms in HLA-G were analysed in the sample cohorts. No association was found between three polymorphisms in HLA-G and PE. However, the frequency of the HLA-G insertion/deletion polymorphism in exon 8 deviated significantly from Hardy-Weinberg expectations in PE off-spring, reflecting an excess of heterozygotes for these polymorphisms in PE offspring. The significance of this deviation is not clear and further genetic analysis will be necessary to confirm this finding and to explore further the candidacy of HLA-G in PE.

Analysis of insulin-like growth factor (IGF)-1-induced enhancement of neurotransmitter release

Analysis of insulin-like growth factor (IGF)-1-induced enhancement of neurotransmitter release

In vivo anabolic effects of parathyroid hormone (PTH) 28-48 and N-terminal fragments of PTH and PTH-related protein on neonatal mouse bones.

We developed a neonatal mouse model to investigate in vivo anabolic effects of intact PTH (1-84) and its two fragments PTH (1-34) and PTH (28-48) and of the N-terminal fragment of PTH-related peptide [PTHrP (1-34)]. Two-day-old mice were injected with low-dose (0.05 microg/g body weight) and high-dose (0.2 microg/g body weight) of each of these peptides daily for 6 or 16 consecutive days. Long bones (tibias and femurs) and mandibular condylar cartilages were harvested. Total DNA and protein were analyzed as parameters for anabolic effects. DNA was increased significantly in tibias only by low doses of PTH (1-84) and PTH (1-34), but by both doses of PTH (28-48). In the cartilages of the mandibular condyles, both doses of all three peptides increased DNA. Total protein was increased in the tibia by the low dose of the three peptides, whereas in the condylar cartilage high doses of PTH (1-34) and PTH (28-48) also caused a 2- to 4-fold increase. When the effects of PTH (1-34) and PTHrP (1-34) on the tibias were compared, it became apparent that PTH (1-34) was more effective than PTHrP (1-34) when injected in low doses, but the latter caused a severalfold increase in DNA and protein at both doses. The outstanding anabolic effect of PTH (28-48) was further investigated using [3H]thymidine autoradiography, analysis of insulin-like growth factor I (IGF-I) protein, and localization of IGF-I messenger RNA (mRNA) by in situ hybridization. PTH (28-48) increased by 3-fold the number of [3H]thymidine-labeled cells in the epiphyseal cartilage of tibias removed from 8-day-old injected mice, and in the proliferative zone of the epiphyseal growth plate of tibias removed from 18-day-old injected mice. Femurs from the latter showed a 20% increase in their IGF-I content. In parallel, only tibias from 18-day-old injected mice showed IGF-I mRNA localization in proliferating chondrocytes, whereas those from vehicle-injected control mice did not exhibit IGF-I mRNA. In summary, our study showed that the neonatal mouse is a sensitive model to examine anabolic effects of different PTH and PTHrP fragments. It also revealed that PTH (28-48) has strong anabolic effects on this model, and suggests that IGF-I might mediate the anabolic effects of PTH (28-48).