For the present, to determine growth hormone(GH) deficiency in patients with short stature, many provocative tests using various pharmacological agents such as glucagon, insulin, clonidine, arginine, growth hormone releasing factor, etc. should be done. These are not only complicated but are also misleading in some patients. In search of a simple and accurate method of detecting GH deficiency that may replace the more complicated provocative tests, we measured basal plasma insulin-like growth factor-I (IGF-I) to see the correlation with the peak GH values in the GH stimulation test. But, in each group of patients with different types of short stature, IGF-I values were poorly correlated. In addition, IGF-I values of the patients with short stature compared to the age- and sex-matched normal ranges showed a significant overlap, and the difference between the proportion of patients with subnormal values in GH deficient patients and non-GH deficient patients was not prominent. Nevertheless, in response to human growth hormone (hGH) administration, both the yearly growth rate and IGF-I levels increased conspicuously. Therefore, even though it may not be feasible to use IGF-I as a single diagnostic measure of patients with short stature, the change in IGF-I values in the follow up of hGH therapy may well represent the response to hGH.
Adolescent ; *Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders/*blood/diagnosis ; Growth Hormone/blood/*deficiency ; Human ; Insulin-Like Growth Factor I/*analysis/metabolism ; Male ; Somatomedins/*analysis

For the present, to determine growth hormone(GH) deficiency in patients with short stature, many provocative tests using various pharmacological agents such as glucagon, insulin, clonidine, arginine, growth hormone releasing factor, etc. should be done. These are not only complicated but are also misleading in some patients. In search of a simple and accurate method of detecting GH deficiency that may replace the more complicated provocative tests, we measured basal plasma insulin-like growth factor-I (IGF-I) to see the correlation with the peak GH values in the GH stimulation test. But, in each group of patients with different types of short stature, IGF-I values were poorly correlated. In addition, IGF-I values of the patients with short stature compared to the age- and sex-matched normal ranges showed a significant overlap, and the difference between the proportion of patients with subnormal values in GH deficient patients and non-GH deficient patients was not prominent. Nevertheless, in response to human growth hormone (hGH) administration, both the yearly growth rate and IGF-I levels increased conspicuously. Therefore, even though it may not be feasible to use IGF-I as a single diagnostic measure of patients with short stature, the change in IGF-I values in the follow up of hGH therapy may well represent the response to hGH.
Adolescent ; *Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders/*blood/diagnosis ; Growth Hormone/blood/*deficiency ; Human ; Insulin-Like Growth Factor I/*analysis/metabolism ; Male ; Somatomedins/*analysis

Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.
Adipokines/metabolism/physiology ; Body Mass Index ; Colorectal Neoplasms/*etiology/prevention & control ; Energy Intake ; Exercise ; Humans ; Insulin Resistance ; Meta-Analysis as Topic ; Obesity/*complications ; Somatomedins/metabolism/physiology ; Weight Loss

PURPOSE: Insulin-like growth factors (IGFs) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with gastrointestinal stromal tumors (GISTs). METHODS: Two hundred-thirteen consecutive patients with GISTs who underwent curative surgery from 5 medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four IGF-1 (+2995C/A, +533C/T, IVS2-16540A/G, Ex4-177G/C) and one IGF-2 (IVS1+1280A/G) gene polymorphisms were determined using a Sequenom MassARRAY system. RESULTS: With a median follow-up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 69.9% and 86.7%, respectively. In a multivariate analysis including age, gender, primary site of disease, pathology, and risk stratification, no significant association was observed between the polymorphism of the IGF-1 and IGF-2 genes and survival. CONCLUSION: None of the five IGF-1 and IGF-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of IGF-1 and IGF-2 gene polymorphisms as a prognostic biomarker for GIST patients.
Apoptosis ; Cell Proliferation ; DNA ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; Humans ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Prognosis ; Somatomedins ; Survival Rate

STATEMENT OF PROBLEM: In the process of bone formation, titanium (Ti) surface roughness is an important factor modulating osteoblastic function. PURPOSE: This study was carried out to determine the effect of different Ti surface on biologic responses of a human osteoblast-like cell line (MG63). MATERIALS AND METHODS: MG63 cells were cultured on S (smooth), SLA (sandblasted largegrit and acid etching), HA (hydroxyapatite) Ti. The morphology and attachment of the cells were examined by SEM. The cDNAs prepared from total RNAs of MG63 were hybridized to a human cDNA microarray (1,152 elements). RESULTS: The appearances of the surfaces observed with SEM were different in the three types of dental substrates. The surface of SLA and HA were shown to be rougher than S. MG63 cells cultured on SLA and HA were cell-matrix interaction. In the expression of genes involved in osseointegration, upregulated genes were bone morphogenetic protein, Villin, Integrin, Insulin-like growth factors in different surfaces. Downregulated genes were fibroblast growth factor receptor 4, Bcl 2-related protein, collagen, CD4 in different surfaces. CONCLUSION: The attachment and expression of key osteogenic regulatory genes were enhanced by surface roughness of the dental materials.
Bone Morphogenetic Proteins ; Cell Line ; Collagen ; Dental Materials ; DNA, Complementary ; Genes, Regulator ; Humans ; Oligonucleotide Array Sequence Analysis ; Osseointegration ; Osteoblasts ; Osteogenesis ; Receptor, Fibroblast Growth Factor, Type 4 ; RNA ; Somatomedins ; Titanium

BACKGROUND: Insulin-like growth factor binding protein 3 (IGFBP3), a member of six proteins with a high affinity for insulin-like growth factors (IGFs), seems to modulate the effects of IGFs on cells and to regulate cell proliferation through the IGF-independent pathway. We assessed the role of IGFBP3 in the colorectal carcinoma detected by cDNA microarray. METHODS: To identify molecular alterations in the colorectal carcinoma, we analyzed gene expression profiles of the colorectal adenocarcinoma by means of a cDNA microarray representing 7,500 genes. Of the differentially expressed genes, the author assessed the insulin-like growth factor binding protein 3 (IGFBP3) gene at the protein level using immunohistochemistry. RESULTS: The expressions of 21 and 16 genes were noted to have more than fivefold increases or decreases in the colonic adenocarcinoma tissue compared with the noncancerous colonic mucosal tissue. The differentially expressed genes include those associated with cell proliferation/apoptosis, signal transduction/transcription, metabolizing enzymes, cytoskeleton, angiogenesis, ion channel, extracellular matrix and others. Of the total 68 cases of colorectal adenocarcinomas observed, 34 cases (50%) showed positive immunohistochemical stainings for IGFBP3. CONCLUSIONS: In this study, it is suggested that IGFBP3 plays a role in colorectal carcinogenesis. And combining an immunohistochemistry with a cDNA microarray can facillitate the rapid characterization of a candidate novel molecular target.
Adenocarcinoma ; Carcinogenesis ; Cell Proliferation ; Colon ; Colorectal Neoplasms* ; Cytoskeleton ; DNA, Complementary* ; Extracellular Matrix ; Immunohistochemistry ; Insulin-Like Growth Factor Binding Protein 3* ; Ion Channels ; Mucous Membrane ; Oligonucleotide Array Sequence Analysis* ; Somatomedins ; Transcriptome

Insulin-like growth factor (IGF)/IGF binding protein (IGFBP) abnormalities may be important in the pathogenesis of growth failure in chronic renal failure (CRF). We induced experimental CRF by 5/6 nephrectomy in Sprague Dawley rats (100 g) and observed for 2 weeks comparing with sham-operated pair-fed control rats (Sham- C). CRF rats gained 30% less height than Sham- C rats (P<0.01). Serum IGFBP profiles by Western ligand blot revealed that IGFBP4 was elevated two fold in CRF rats (P<0.01 vs. Sham-C). However, IGFBP4 mRNA levels in liver or skeletal muscle were not different in two groups. To determine if the increase of serum IGFBP4 in CRF retarded the growth of cartilage, epiphyseal chondrocytes were isolated from CRF or control rats and cultured in the presence of control or CRF rat sera. Incubation with 10% CRF serum reduced proliferations of normal chondrocytes and L6 rat skeletal muscle cells. In contrast, 10% CRF serum did not inhibit the growth of CRF chondrocytes. Rat sera from two groups were separated into two different fractions, high (>10 kDa, containing IGFBPs) and low (<10 kDa, containing free IGF) molecular weight fractions using a gel filtration column. Both fractions obtained from CRF sera decreased the growth of control chondrocytes up to 40% compared with those from control sera. We suggest that the pathogenesis of growth failure in CRF may be involved in the increase of circulating IGFBP4 as well as the unidentified small molecular weight uremic serum factors which block the growth of chondrocytes in growth plate.
Animals ; Cell Proliferation ; Cells, Cultured ; Chondrocytes/*cytology/metabolism ; Insulin-Like Growth Factor Binding Protein 4/analysis/*blood/genetics ; Kidney Failure, Chronic/*blood/metabolism/physiopathology ; Liver/chemistry ; Male ; Muscle, Skeletal/chemistry ; RNA, Messenger/analysis/metabolism ; Rats ; Rats, Sprague-Dawley ; Somatomedins/analysis/metabolism