• Title, Summary, Keyword: Insulin-like Growth Factors

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Insulin-Like Growth Factors and Their Binding Proteins in Tumors and Ascites of Ovarian Cancer Patients: Association With Response To Neoadjuvant Chemotherapy

  • Yunusova, Natalia V;Villert, Alisa B;Spirina, Liudmila V;Frolova, Alena E;Kolomiets, Larisa A;Kondakova, Irina V
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5315-5320
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    • 2016
  • Purpose: Tumor cell growth and sensitivity to chemotherapy depend on many factors, among which insulin-like growth factors (IGFs) may play important roles. The aim of the present study was to evaluate the levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in primary tumors and ascites as predictors of response to neoadjuvant chemotherapy in ovarian cancer (OC) patients. Materials and Methods: Tumor tissue samples and ascitic fluid were obtained from 59 patients with advanced OC. The levels of IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A were determined using ELISA kits. Taking into account the data on expression of these IGF-related proteins and outcome, logistic regression was performed to identify predictors of response to neoajuvant chemotherapy. Results: Human ovarian tumors expressed IGFs, IGFBP-3, IGFBP-4 and PAPP-A and these proteins were also present in ascites fluid and associated with its volume. IGFs and IGFBPs in ascites and soluble PAPP-A might play a key role in ovarian cancer progression. However, levels of proteins of the IGF system in tumors were not significant predictors of objective clinical response (oCR). Univariate analysis showed that the level of IGF-I in ascites was the only independent predictor for oCR. Conclusion: The level of IGF-I in ascites was shown to be an independent predictor of objective clinical response to chemotherapy for OC patients treated with neoadjuvant chemotherapy and debulking surgery.

ENDOCRINE CHANGES AND CIRCULATING INSULIN-LIKE GROWTH FACTORS IN NEWBORN CALVES FED COLOSTRUM, MILK OR MILK REPLACER

  • Lee, C.-Y.;Head, H.H.;Feinstein, C.R.;Hayen, J.;Simmen, F.A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.8 no.1
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    • pp.51-58
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    • 1995
  • To examine whether colostral growth factors are transferred to the general circulation, concentrations of plasma cortisol, insulin, prolactin, growth hormone, insulin-like growth factors(IGFs) -I and -II, IGF-binding proteins(IGFBPs) and total protein were measured in newborn calves fed colostrums, milk of milk replacer before and after feeding at 12 h intervals during the first two days after birth. Plasma protein concentrations increased with time after than in milk- or milk replacer-fed calves. The mean protein concentration was greater in colostrum-fed than in milk- or milk replacer-fed calves. Plasma cortisol levels transiently declined after each feeding regardless of the type of diet, while insulin levels tended to increase. Mean concentrations of these hormones did not differ between dietary groups, nor did they change with time after birth. Plasma concentrations of prolactin and growth hormone did not differ between dietary groups and also did not change with time after birth or after feeding. Concentrations of IGF-I and IGF-II transiently increased at the second feeding period, but these, as well as plasma IGFBP profiles, were not different between groups or before and after feeding. Results did not indicate significant transfer of colostral growth factors across the newborn ruminant small intestine.

Changes in Serum Insulin-Like Growth Factor Binding Protein-5 of Osteopenia (골감소증 환자의 혈청중 Insulin-Like Growth Factor Binding Protein-5의 변화)

  • Kim, Young;Nam, Taek-Jeong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.3
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    • pp.493-499
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    • 2000
  • 골감소증 환자의 혈청중에 존재하는 IGFBP-5의 존재와 변화를 검토한 결과, 골감소즈 환자에서는 정상 대조군에 비해 IGFBP-5가 감소하였는데 이 변화는 IGFBP-5의 분해효소가 작용하기 때문인 것으로 나타났다. IGFBP-5에 작용하는 단백질분해효소 저해제중 metallo계인 EDTA 및 1,10-phenanthroline과 seriner계인 aprotinin, heparin, heparin cofactor 2(HC2), heparine+HC2가 IGFBP-5에 대해 저해효과가 크므로 metalloprotease이면서 serine protease의 성질을 가지는 효소들이 IGFBP-5에 작용하였다. IGF-I과 IGF-II 그리고 insulin은 효소 활성에 아무런 영향이 없었다. IGFBP-5의 zymography에서 정상인과 골감소증 환제어서 180 kDa 크기의 band가 나타났고, gelatin zymography에서 정상 대조군의 경우 66 kDa과 97 kDa 정도의 band가 확인되었고 골감소증 환자의 경우는 69 kDa의 band가 확인되었다.

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Growth Stimulation and Inhibition of Differentiation of the Human Colon Carcinoma Cell Line Caco-2 with an Anti-Sense Insulin-Like Growth Factor Binding Protein-3 Construct

  • YoonPark, Jung-Han
    • BMB Reports
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    • v.32 no.3
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    • pp.266-272
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    • 1999
  • The insulin-like growth factor (IGF) system consisting of IGF-I, IGF-II, IGF-receptors, and IGF-binding proteins (IGFBP) regulates the proliferation of a variety of cancer cell types. To examine whether a decrease in endogenous IGFBP-3 stimulates proliferation or inhibits differentiation, Caco-2 cells, a human colon adenocarcinoma cell line, were stably transfected with an anti-sense IGFBP-3 expression construct or pcDNA3 vector as control. Accumulation of IGFBP-3 mRNA and secretion of IGFBP-3 into serum-free conditioned medium, 9 days after plating, were significantly lower in Caco-2 cell clones transfected with anti-sense IGFBP-3 cDNA compared to the controls. The anti-sense clones grew at a similar rate to the controls for 8 days after plating, but achieved a higher final density between days 10 and 12. The levels of sucrase-isomaltase mRNA, a marker of enterocyte differentiation of Caco-2 cells, were lower in the anti-sense clones examined on day 9. In conclusion, proliferation of Caco-2 cells can be stimulated by lowering endogenously-produced IGFBP-3.

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Effects of Safflower Seeds on the Serum Levels of Insulin-like Growth Factors, Insulin-like Growth Factor Binding Protein-3 and BALP in Osteoporosis Induced-ovariectomized Rats (흰쥐의 난소제거로 유발한 골다공증에 대한 홍화씨의 IGFs, IGF binding protein-3 그리고 BALP에 대한 혈청내 효과)

  • Kim, Soo-mi;Park, In-hyuk;Kim, Nam-soo
    • Journal of Veterinary Clinics
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    • v.20 no.3
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    • pp.263-273
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    • 2003
  • This study was carried out to investigate the effects of the Korean Safflower (Carthamus inctorius L) seed powder on serum level of hormones and trabecula area during the recovery from osteoporosis induced ovariectomized rats. Four month-old rats were ovariectomized (OVX), remained untreated for 8 weeks, and were subsequently administered safflower seed (0.03 g/kg) every other day 30 for days. We examined the effects of treated safflower seed every 10 days on ovariectomy-related changes in Insulin-like Growth Factors, Insulin-like Growth Factor binding protein-3 (IGFBP-3), Estrogen, Bone-specific alkaline phosphotase, Calcium, and Phospotase in the serum, and also histomorphology of the proximal fibula metaphysis and femur/body weight rate. Ten and 20 days after safflower seed treatment in OVX rats, serum levels of IGF-I, -II and IGFBP-3 were not different from the Sham and OVX groups. In 30 days, serum levels of IGF-I,-II and IGFBP-3 were higher after safflower seed treatment in OVX rats as compared to the other two groups (p<0.05). Bone alkaline phosphatase levels were increased through safflower seed treatment in OVX rats compared to the other two groups in 30 days. There were no differences between OVX and safflower seed treated OVX rats in serum levels of estrogen and femur/body weight rate, but estrogen levels for the sham group were higher than for the other two groups. The safflower seed is increased to serum levels of IGFs, IGFBP-3 and BALP of osteoporosis induced by ovariectomized rats. Thus, we conclude that the safflower seed is a possible role for improvement of osteoporosis induced-ovariectomized rats.

Effect of progesterone on insulin-like growth factors(IGFs) and IGF-binding proteins(IGFBPs) in female rat (암컷 랫트에서 Progesterone투여가 Insulin-like Growth Factors(IGFs) 및 IGF-binding proteins(IGFBPs)에 미치는 효과)

  • Jin, Song-Jun;Park, Soo-Hyun;Kang, Chang-Won
    • Korean Journal of Veterinary Research
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    • v.42 no.4
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    • pp.459-467
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    • 2002
  • The sex steroid hormone progesterone is essential for normal development and maturation of the endometrium in preparation for the embryo implantation and the maintenance of pregnancy. Insulin-like growth factor (IGF) system that is composed of IGF-I, IGF-II, IGF binding proteins (IGFBPs) is also involved in the maintenance of pregnancy. In addition, liver, kidney, and uterus is a target tissue for IGF system. However, the effect of exogenous progesterone on IGF system was not elucidated in female rats. Therefore, we investigated the effect of progesterone on insulin-like growth factors (IGFs) and IGF-binding proteins in serum, liver, kidney, and uterus in female ovariectomized rats. IGFs concentration was measured by radioimmuoassay (RIA) and IGFBPs levels by western ligand blotting(WLB). IGF-I concentration was increased in serum, liver, and uterus, but not in kidney of progesterone-treated ovariectomized rats, compared to control (P<0.05). IGF-II concentration was decreased in liver, but not in serum, kidney, and uterus of progesterone-treated rats, compared to control (P<0.05). IGFBP-3 was increased in serum, but not in liver of progesterone-treated rats, compared to control. IGFBP-2 was decreased in kidney, but not in others tissues of progesterone-treated rats, compared to control. These results suggest that progesterone may exert diverse physiological functions via the tissue-specific regulation of IGFs/IGFBPs system in female rats.

Insulin-like Growth Factor-1 (IGF-1) Gene Expression Is Enhanced under Hypothermia but Depressed under Additional Ischemic Stimulus

  • Kwon, O-Yu;Kwon, Kisang;Yu, Kweon;Kim, Seung-Whan
    • Biomedical Science Letters
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    • v.21 no.2
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    • pp.126-130
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    • 2015
  • There are several studies that show hypothermia improves cellular ischemia damages on experimental and clinical bases. However, its exact molecular mechanisms are unclear. In this study, we demonstrate that hypothermia induced insulin-like growth factor 1 (IGF1) gene expression, and its expression was dramatically decreased under ischemic insults. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both the phosphorylation of $eIF2{\alpha}$ (eukaryotic translation initiation factor 2 alpha) and ATF6 (activating transcription factor-6) proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. We suggest that hypothermia-treated IGF1 gene expression after ischemia may show a good possibility for the development of treatments and diagnostic methods in cerebral ischemic damages.

Milk-Derived Growth factors as Neutraceuticals

  • Kang, Shin-Ho
    • Journal of Dairy Science and Biotechnology
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    • v.25 no.1
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    • pp.27-31
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    • 2007
  • Colostrum has lots of bioactive components and many growth factors including insulin-like growth factors, transforming growth factors and epidermal growth factor. Colostrum and milk derived growth factors widely mediate the growth of overall development and could be used as treatment of gastrointestinal disorder, wound repair process, bioacrivity in the neonatal GI tract and induction of oral tolerance. It is possible that milk derived growth factors as potential neutraceuticals for the specific consumers may have a great role in future food industry.

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The roles of PKC-δ on the regulation of insulin-like growth factor(IGF)-I and insulin-Like growth factor binding protein-3 secretion by all-trans retinoic acid in MCF-7 cell (MCF-7 cell에서 all-trans retinoic acid에 의한 insulin-like growth factor-I와 insulin-like growth factor binding protein-3 분비조절에 있어서 PKC-δ의 역할)

  • Lee, Sun-Mi;Kim, Sang-Hoon;Choi, Kwang-Soo;Kang, Chang-Won
    • Korean Journal of Veterinary Research
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    • v.46 no.2
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    • pp.97-105
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    • 2006
  • All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). $10^{-7}M$ AtRA activated PKC-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA-induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-${\delta}$ activity.

Effects of Epidermal Growth Factor (EGF) and Insulin-like Growth Factor-1 (IGF-1) on Maturation of Bovine Follicular Oocytes In Vitro (Epidermal Growth Factor(EGF)와 Insulin-like Growth Factor-1(IGF-1)이 소 난포란의 체외성숙에 미치는 영향)

  • 윤종택;정영호;한기영;최선호
    • Journal of Embryo Transfer
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    • v.13 no.3
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    • pp.245-249
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    • 1998
  • The purpose of this study was to evaluate the effects of growth factors such as epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) on maturation of bovine follicular oocytes in vitro. Oocytes were recovered from the ovaries of slaughtered Hanwoos. The oocytes were matured in TCM 199 at 39$^{\circ}C$, 5% $CO_2$ in air. Growth factors were added to maturation medium as follows: control (no serum), EGF (10ng/m1, 50ng/ml or 100ng/m1), IGF-1 (100ng/m1) and EGF (50ng/ml) + IGF-1 (100ng/m1). The oocytes were placed onto a slide and stained with aceto-orcein dye. Nuclear maturation was evaluated and classified as germinal vesicle breakdown (GVBD), metaphase-I (MI) or metaphase-ll(Mll). Maturation rates were 37.9% (control), 45.8% (EGF, 10ng/m1), 55.8% (EGF, 50ng/ml), 44.4% (EGF, 100ng/m1), 46.7% (IGF-1, 100ng/m1) and 67.0% (IGF-1+EGF). The highest group developed to Mll stage was IGF-1+EGF treatment group (p<0.05). Therefore, nuclear maturation of bovine oocytes were affected by both of growth factors, and it seems to have a mutual activity between them.

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