The objective of this proposal is to determine the prognostic role of expression of Insulin-Like Growth factor II in breast cancer. IGF-II is a potent mitogen for breast tumor epithelium, and is expressed in the stroma of invasive breast cancers. In this study, we analyzed expression of IGF-II mRNA and protein in two separate series of patients with invasive breast cancer, and compared the result with other clinical parameters, prognostic indicators and patient outcome. IGF-II mRNA and protein expression were easily detected in the majority of the 193 cases that were informative and had complete clinical follow up. While analysis of the cases from the two data sets individually showed that IGF-II expression was associated with clinical outcome depending on hormone receptor status. However, IGF-II expression by itself was not a prognostic indicator, and the relationship with hormone receptor status was lost when the separate data sets were analyzed together. We were unable to prove our initial hypothesis
TY - JOUR. T1 - Insulin-like growth factor-II in nonislet cell tumors associated with hypoglycemia. T2 - Increased levels of messenger ribonucleic acid. AU - Lowe, William L.. AU - Roberts, Charles T.. AU - Leroith, Derek. AU - Rojeski, Maria T.. AU - Merimee, Thomas J.. AU - Fui, Serge Teng. AU - Keen, Harry. AU - Arnold, Dagmar. AU - Mersey, James. AU - Gluzman, Sheldon. AU - Spratt, Daniel. AU - Eastman, Richard C.. AU - Roth, Jesse. PY - 1989/12. Y1 - 1989/12. N2 - The role of insulin-like growth factor-II (IGFII) in the hypoglycemia associated with nonislet cell tumors is controversial. In this study we have addressed this question by measuring the IGF-II mRNA levels in extracts of these tumors. Hybridization of a 32P-labeled IGF-II cDNA to a Northern blot of RNA from three nonislet cell tumors associated with hypoglycemia (a hemangiopericytoma, fibrosarcoma, and malignant mesenchymal tumor) demonstrated six hybridizing bands, 6.8, 5.6, 4.7, 3.6, 2.6, and 2.1 kilobases in length. These ...
TY - JOUR. T1 - Measurement of insulin-like growth factor-II in physiological fluids and tissues. II. extraction and quantification in rat tissues. AU - Lee, Wei Hua. AU - Bowsher, Ronald R.. AU - Apathy, John M.. AU - Smith, Michele C.. AU - Henry, David P.. PY - 1991/2. Y1 - 1991/2. N2 - The tissue distribution and developmental patterns of insulin-like growth factor-II (IGF-II) have not been investigated in rat tissues, primarily because of the lack of an efficient extraction method for IGF-II and a sensitive RIA. IGF- II was extracted from rat tissues by formic acid, and the extract was heated at an acidic pH and treated with acetone. The removal of binding proteins was demonstrated by fast protein liquid chromatography size exclusion column and the elimination of a dilutional bias in the RIA. Using rat IGF-II as standard, we optimized a RIA for the quantification of IGF-II in rat tissues. In adult rats, IGF-II was found in all 15 tissues examined, with the highest concentration in the ...
Insulin Like Growth Factor II (Somatomedin A or T3M 11 Derived Growth Factor or IGF2) - Pipeline Review, H2 2017 Size and Share Published in 2017-08-22 Available for US$ 3500 at Researchmoz.us
Insulin-like growth factor-1 (IGF-1) is structurally homologous to proinsulin. IGF-1 is produced by several cell types and may have autocrine, paracrine and endocrine functions. IGF-1 is a potent mitogen that mediates the growth-promoting activities of growth hormone postnatally. It also plays a role during embryonic growth and differentiation. Recombinant mouse IGF-1 is a 7.6 kDa protein containing 70 amino acid residues. IGF-1 receptor is a disulfide-linked heterotetrameric transmembrane glycoprotein with an intracellular tyrosine kinase domain ...
Bevan, S. J., Parry-Billings, M, Opara, Elizabeth, Liu, C. T., Dunger, D. B. and Newsholme, E. A. (1992) The effect of insulin-like growth factor II on glucose uptake and metabolism in rat skeletal muscle in vitro. Biochemical Journal, 286(2), pp. 561-565. ISSN (print) 0264-6021 ...
Loss of Imprinting of Insulin-like Growth Factor-II in Wilms Tumor Commonly Involves Altered Methylation but not Mutations of CTCF or Its Binding ...
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IDDM2-encoded predisposition to type 1 diabetes has recently been mapped to the minisatellite or variable number of tandem repeat (VNTR) locus upstream of the insulin and insulin-like growth factor II genes on human chromosome 11p15.5. In a UK case-control study (n=228 sporadic diabetics; n=441 healthy controls), we show here that the genotype homozygous for VNTR class I alleles is predisposing to disease (RR=2.68), and VNTR class III alleles are dominantly protective (RR=0.37). In 722 diabetic families from the UK (n=356), USA (n=173), Denmark (n=55) and Sardinia (n=138), we have analysed the transmission of class I alleles to diabetic offspring from class I/III heterozygous parents. We confirm that in families from the USA, class I alleles are transmitted preferentially from fathers. However, in family data sets from the UK, Denmark and Sardinia, the reverse is true and maternal transmission is stronger. Furthermore, in the UK family data set, the difference between maternal and paternal ...
The insulin-like growth factors possess growth-promoting activity. Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development. IGF-II is influenced by placental lactogen. Also involved in tissue differentiation. Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation. In adults, involved in glucose metabolism in adipose tissue, skeletal muscle and liver.
J:58580 van Kleffens M, Groffen CA, Dits NF, Lindenbergh-Kortleve DJ, Schuller AG, Bradshaw SL, Pintar JE, Zwarthoff EC, Drop SL, van Neck JW, Generation of antisera to mouse insulin-like growth factor binding proteins (IGFBP)-1 to -6: comparison of IGFBP protein and messenger ribonucleic acid localization in the mouse embryo. Endocrinology. 1999 Dec;140(12):5944-52 ...
J:58580 van Kleffens M, Groffen CA, Dits NF, Lindenbergh-Kortleve DJ, Schuller AG, Bradshaw SL, Pintar JE, Zwarthoff EC, Drop SL, van Neck JW, Generation of antisera to mouse insulin-like growth factor binding proteins (IGFBP)-1 to -6: comparison of IGFBP protein and messenger ribonucleic acid localization in the mouse embryo. Endocrinology. 1999 Dec;140(12):5944-52 ...
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Reagents and antibodies. Mouse Laminin-1, Lipofectin, LipofectAMINE, and LipofectAMINE 2000 were purchased from Invitrogen (Carlsbad, CA). Recombinant human IGF-I or IGF-II (rhIGF-II) was purchased from R&D System, Inc. (Minneapolis, MN) or Austral Biologics (San Ramon, CA), respectively. Human FN was purified as described ( 33). Bovine serum albumin (BSA) was purchased from Sigma (St. Louis, MO). Wortmannin was purchased from Calbiochem (La Jolla, CA).. The following monoclonal antibodies (mAbs) were used: to human β1 integrin P4C10 (Chemicon, Temecula, CA), clone-18 (BD Biosciences, San Jose, CA), and TS2/16 [American Type Culture Collection (ATCC), Manassas, VA]; to chicken β1 integrin W1B10 (Sigma Chemical Co., St. Louis, MO); to human β4 integrin A9 (kindly provided by Dr. L. Shaw); to hemagglutinin 12CA5 (ATCC); to a vascular endothelial surface protein 1C10 (Life Technologies, Inc., Gaithersburg, MD); to c-myc; to β-tubulin (Sigma). The following rabbit polyclonal antibodies were ...
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Insulin-like Growth Factor II (IGF-II) analogues in which at least one of R37 and R38 is replaced with another amino add residue, the most preferred being IGF-II R37Q R38Q, can readily be produced in E. coli, unlike natural IGF-II, which is cleaved on secretion. The analogues retain activity on the type I and type II IGF receptors but have lower affinity for the insulin receptor; they are therefore more specific in their action.
We studied the expression of the N-myc proto-oncogene and the insulin-like growth factor-II (IGF-II) gene in human fetuses of 16-19 gestational wk. Both genes have specific roles in the growth and differentiation of embryonic tissues, such as the kidney and neural tissue. Since continued expression of N-myc and IGF-II mRNAs is also a characteristic feature of Wilms tumor, a childhood neoplasm of probable fetal kidney origin, we were particularly interested in the possibility that their expression might be linked or coordinately regulated in the developing kidney. Expression of N-myc mRNA was observed in the brain and in the kidney by Northern hybridization analysis. In in situ hybridization of the kidney, N-myc autoradiographic grains were primarily located over epithelially differentiating mesenchyme while most of the mesenchymal stromal cells showed only a background signal with the N-myc probe. N-myc mRNA was detectable throughout the developing brain with a slight accentuation in the ...
... is a blood-clotting disorder that results in excessive or prolonged bleeding after an injury or surgery. Factor II is one of 13 proteins involved in proper formation of blood clots. Blood clots are needed to heal wounds, form scabs, and stop bleeding. When factor I levels are low or absent, the blood does not clot correctly, leading to excessive bleeding. Factor II deficiency runs in families and affect both males and females equally. The main symptom of factor II deficiency is excessive and abnormal bleeding. This may occur after childbirth, surgery, trauma, and with menstruation (periods). Bleeding can also occur in the muscles, joints, the mouth, the gut, or, infrequently, the brain. Easy bruising and nosebleeds are also common. Factor II deficiency can be diagnosed by a physician using blood tests. Treatment for factor II deficiency is largely based on controlling bleeding and treating any underlying conditions that contribute to excessive bleeding. When necessary, ...
Insulin-like growth factor II (IGF-II) plays a key role in mammalian growth and is involved in stimulating fetal cell division, differentiation, and metabolic regulation. IGF-II is considered a candidate gene for genetic markers of growth and carcass traits. Therefore, in this study, the associations of single nucleotide polymorphisms (SNPs) in the IGF-II gene region with growth and ... more ...
Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon, and liver cancer. As IGF-II can deliver a mitogenic signal through both IGF-IR and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is a potential alternative option to IGF-IR-directed agents. Using a Fab-displaying phage library and a biotinylated precursor form of IGF-II (1-104 amino acids) as a target, we isolated Fabs specific for the E-domain COOH-terminal extension form of IGF-II and for mature IGF-II. One of these Fabs that bound to both forms of IGF-II was reformatted into a full-length IgG, expressed, purified, and subjected to further analysis. This antibody (DX-2647) displayed a very high affinity for IGF-II/IGF-IIE (K(D) value of 49 and 10 pmol/L, respectively) compared with IGF-I (approximately 10 nmol/L) and blocked binding of IGF-II to IGF-IR, IR-A, a panel of ...
42. De Bleser, P., P. Hannes, S. Van Buul-Offers, C. Hoogerbrugge, C. Van Schravendijk, T. Niki, V. Rogiers, J. Van den Brande, E. Wisse, and A. Geerts. 1995. Increased insulin-like growth factor-II/mannose 6-phosphate receptor on fibrotic rat fat-storing cells facilitates activation of latent transforming growth factor- . In Cells of the Hepatic sinusoid. E. Wisse, D.L. Knook, and K. Wake, editors. The Kupffer Cell Foundation, Leiden. 383-385 ...
BioAssay record AID 1078972 submitted by ChEMBL: Inhibition of human IGF1R catalytic domain expressed in baculovirus assessed as substrate phosphorylation using fluorescence-labelled peptides as substrate at 0.06 uM after 90 mins by microfluidic peptide phosphorylation assay.
References for Abcams Recombinant human IGF1 protein (ab123776). Please let us know if you have used this product in your publication
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TY - JOUR. T1 - Effect of Ethanol on Insulin‐Like Growth Factor‐II Release from Fetal Organs. AU - Mauceri, Helena J.. AU - Lee, Wei‐Hua ‐H. AU - Conway, Sonya. PY - 1994/2. Y1 - 1994/2. N2 - This study examines the effect of ethanol (ETOH) exposure and nutrient restriction on the release of insulin‐like growth factor (IGF)‐II from 18‐ and 20‐day explanted fetal organs. Fetuses were exposed to ETOH (E) in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Control fetuses were offsprings of dams either pair‐fed (P) a control liquid diet or ad libitum (A) fed a standard pelleted lab chow. Brain, heart, kidney, liver, lung, muscle, and placenta of fetuses from the same litter were pooled and explanted, and IGF‐II concentration in explanted media was analyzed by radioimmunoassay. Maternal and fetal weights were determined during pregnancy and at sacrifice, respectively, to evaluate the influence of ETOH on growth. Both maternal and fetal weights ...
The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulinlike growth factor-binding proteins) and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism and reproduction (e.g., germ cell development and fertilisation), real-time reverse transcription polymerase chain reaction assays for quantification of equine insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were developed. The assays were sensitive: 192 copies/μL and 891 copies/μL for insulin-like growth factor 1 receptor, messenger ribonucleic acid and insulin ...
The present study demonstrates that IR-A is a physiological receptor for IGF-II. Previously it was believed that most, if not all, biological effects of IGF-II in cells were mediated by IGF-I-R. IGF-II-R, which also binds mannose-6-phosphate residues, is devoid of tyrosine kinase activity and is not believed to have either metabolic or mitogenic signaling potential. Most studies have indicated that the IR, which is homologous to the IGF-I-R, binds IGF-II with a relatively low affinity (1 to 5% that of insulin) (45). However, there is evidence that in certain instances the IR can bind IGF-II with high affinity. "Atypical" IRs, which bind IGF-II with unusually high affinity, have been found in IM-9 lymphoblasts, immature erythrocytes (18), and fetal tissues (including human placenta and brain, and chicken embryo fibroblasts) (19). Furthermore, other studies suggest that during mouse fetal development, the growth promoting effect of IGF-II is mediated in part by signaling through the IR (28). By ...
The present study demonstrates that IR-A is a physiological receptor for IGF-II. Previously it was believed that most, if not all, biological effects of IGF-II in cells were mediated by IGF-I-R. IGF-II-R, which also binds mannose-6-phosphate residues, is devoid of tyrosine kinase activity and is not believed to have either metabolic or mitogenic signaling potential. Most studies have indicated that the IR, which is homologous to the IGF-I-R, binds IGF-II with a relatively low affinity (1 to 5% that of insulin) (45). However, there is evidence that in certain instances the IR can bind IGF-II with high affinity. "Atypical" IRs, which bind IGF-II with unusually high affinity, have been found in IM-9 lymphoblasts, immature erythrocytes (18), and fetal tissues (including human placenta and brain, and chicken embryo fibroblasts) (19). Furthermore, other studies suggest that during mouse fetal development, the growth promoting effect of IGF-II is mediated in part by signaling through the IR (28). By ...
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Conduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to unhealthy diet. Early‐life diet also associates with DNA methylation of the insulin‐like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high‐fat and ‐sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early‐onset persistent (EOP) versus low CP youth. Read the Commentary on this article at doi ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
The insulin‐like growth factor (IGF)‐system includes insulin‐like growth factors I and II (IGF‐I and IGF‐II) along with the type I (IGF‐1R) and type II (IGF2R) cell‐surface receptors, the insulin receptor (IR) and circulating IGF‐binding proteins (IGFBPs) (Denley et al, 2005). The biological actions of the IGFs are mediated by IGF‐1R and IR, leading to cell growth, differentiation and survival. Their distribution and activity is controlled via high‐affinity association with IGFBPs, and the binding sites on IGFs for IGFBPs have been delineated in detail by structural studies (Headey et al, 2004; Carrick et al, 2005; Sitar et al, 2006). In mammals, the activity of IGF‐II (but not IGF‐I) is further moderated by IGF2R, which sequesters IGF‐II for internalization and degradation. IGF2R is classed as a growth inhibitor, with loss of function causing increased growth (Foulstone et al, 2005). In line with this, Igf2r is a putative tumour suppressor gene and mutations have been ...
The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "axis") consists of two cell-surface receptors (IGF1R and IGF2R), two ligands (Insulin-like growth factor 1 (IGF-1) and Insulin-like growth factor 2 (IGF-2)), a family of six high-affinity IGF-binding proteins (IGFBP-1 to IGFBP-6), as well as associated IGFBP degrading enzymes, referred to collectively as proteases. The IGF "axis" is also commonly referred to as the Growth Hormone/IGF-1 Axis. Insulin-like growth factor 1 (IGF-1, or sometimes with Roman Numeral as IGF-I) is mainly secreted by the liver as a result of stimulation by growth hormone (GH). IGF-1 is important for both the regulation of normal physiology, as well as a number of pathological states, including cancer. The IGF axis has been shown to play roles in the promotion of cell proliferation ...
Pre- and postnatal growth failure can be caused by mutations in the IGF1 (insulin-like growth factor 1) or IGF1R (insulin-like growth factor 1 receptor) genes. Autosomal recessive mutations in IGF1 cause insulin-like growth factor I deficiency (MIM 608747), which is characterized by microcephaly, intellectual disability, and deafness in addition to the growth failure. Autosomal dominant mutations in IGF1R cause insulin-like growth factor I, resistance to (MIM 270450). It is associated with partial IGF1 resistance, pre- and postnatal growth failure, microcephaly, and in some cases modest intellectual disability. Autosomal recessive IGF1R mutations have been found in a few patients. This results in a more severe growth delay and additional developmental abnormalities.. Read less ...
Protein undernutrition is characterized by growth failure in young growing animals. Current evidence suggests that biosynthesis of insulin-like growth factor (IGF)-I and IGF-binding protein 1 (IGFBP-1) are key control points for nutritional regulation of growth. Here we examined the role of amino acid limitation in regulating the IGFBP-1 expression in the hepatic cell line. Our data show that leucine limitation strongly induces IGFBP-1 without affecting IGF-I and IGF-II expression in human HepG2 cells and in isolated rat hepatocytes. Depletion of arginine, cystine and all essential amino acids leads to induction of IGFBP-1 mRNA and protein expression in a dose-dependent manner. IGFBP-1 expression is significantly induced by leucine concentration in the range of that observed in the blood of rats fed a low-protein diet or in humans affected by kwashiorkor. Moreover, treatment of HepG2 cells with amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats ...
Extracellular matrix (ECM)1 serves as the immediate microenvironment for interactions with the cell surface, besides providing the structural support for all tissues. The ECM is not static. Rather, it is dynamic in nature with a continuous turnover of its protein constituents and growth factor pools. A major determinant of ECM turnover and integrity is the extracellular proteolytic balance between secreted matrix metalloproteinases (MMPs) and their biological inhibitors (TIMPs) (for reviews see Matrisian 1992; Denhardt et al. 1993; Mignatti and Rifkin 1993). The function of extracellular proteolysis extends beyond ECM degradation to the processing of cell surface receptors and ligands and release of protein-bound growth factors (for review see Werb 1997). Therefore, it is conceivable that extracellular proteolytic activity within the cellular microenvironment can directly impact cell proliferation. Despite transgenic studies showing that cellular proliferation is altered by ectopic expression of ...
Hypoglycaemia is defined as a blood glucose concentration below 3.0 mmol/litre, which is clinically important because of its effect on brain function. Much the commonest cause is excessive (in relation to intake of food and drink) administration of insulin or sulphonylurea drugs to patients known to have diabetes, but there are many rarer causes including insulinoma, toxins (alcohol), organ failure (hepatic), endocrine diseases (adrenal insufficiency, pituitary insufficiency), non-islet cell tumour hypoglycaemia, autoimmune insulin syndrome, factitious or felonious administration of insulin/sulphonylureas, and infections (malaria)....
J Clin Endocrinol Metab. 2000 Apr;85(4):1686-94.. Mauras N, OBrien KO, Welch S, Rini A, Helgeson K, Vieira NE, Yergey AL.. Division of Endocrinology, Nemours Childrens Clinic, Jacksonville, Florida 32207, USA. [email protected] We examined the effects of recombinant human (rh) insulin-like growth factor I (IGF-I) vs. rhGH in a variety of metabolic paths in a group of eight severely GH-deficient young adults using an array of contemporary tools. Protein, glucose, and calcium metabolism were studied using stable labeled tracer infusions of L-[1-13C]leucine, [6,6-2H2]glucose, and 42Ca and 44Ca; substrate oxidation rates were assessed using indirect calorimetry; muscle strength was determined by isokinetic and isometric dynamometry of the anterior quadriceps, as well as growth factors, hormones, glucose, and lipid concentrations in plasma before and after 8 weeks of rhIGF-I (60 microg/kg, sc, twice daily), followed by 4 weeks of washout, then 8 weeks ofrhGH (12.5 microg/kg-day, sc); the ...
Purpose: We demonstrated that IGFBP-3 stimulates hematopoietic stem cells (HSC) to differentiate into endothelial cells, form capillaries, and stabilize the vasculature (Chang, et al, PNAS 2007). Local IGFBP- 3 production is increased by hypoxia and facilitates the homing of HSC to areas of injury. In the circulation, IGFBP-3 is bound to HDL. In this study, we investigated the signaling pathways responsible for the robust migratory effects of IGFBP-3.. Methods: The effects of IGFBP-3 on NO generation in human vascular precursors (CD 34+, CD14−), human lung microvascular endothelial cells, and human umbilical vein endothelial cells were examined using DAF-FM fluorescence. Western analysis was use for detection of eNOS and vasodilator-stimulated phosphoprotein (VASP), which redistributes to lamellipodia forming an active motor complex that supports motility and is phosphorylated in response to NO. Localization of VASP was performed by immunohistochemistry. SK-1 was assessed following IGFBP-3 ...
Luteolin is a 3,4,5,7-tetrahydroxyflavone found in various fruits and vegetables. We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest. The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in HT-29 cells. In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway, cells were cultured with or without 60 μmol/L luteolin and/or 10 nmol/L IGF-I. Cell proliferation, DNA synthesis, and IGF-IR mRNA levels were evaluated by a cell viability assay, [3H]thymidine incorporation assays, and real-time polymerase chain reaction, respectively. Western blot analyses, immunoprecipitation, and in vitro kinase assays were conducted to evaluate the secretion of IGF-II, the protein expression and activation of IGF-IR, and the association of the p85 subunit of phophatidylinositol-3 kinase (PI3K) with IGF-IR, the phosphorylation of Akt and
Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on somatotropin. It is believed to be a major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults". In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7. In both organisms, Igf2 is imprinted, with expression resulting favourably from the paternally inherited allele. However, in some human brain regions a loss of imprinting occurs resulting in both IGF2 and H19 being transcribed from both parental alleles. The protein CTCF is involved in repressing expression ...
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The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire
Objective Insulin and the insulin-like growth factor (IGF) system regulate growth and are involved in determining muscle mass, strength and body composition. We hypothesised that IGF-I and IGF-II are associated with improved, and insulin with worse, physical performance in old age. Methods Physical performance was measured using the get-up and go timed walk and flamingo balance test at 63-86 years. We examined prospective associations of insulin, IGF-I, IGF-II and IGFBP-3 with physical performance in the UK-based Caerphilly Prospective Study (CaPS; n = 739 men); and cross-sectional insulin, IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in the Boyd Orr cohort (n = 182 men, 223 women). Results In confounder-adjusted models, there was some evidence in CaPS that a standard deviation (SD) increase in IGF-I was associated with 1.5% faster get-up and go test times (95% CI: −0.2%, 3.2%; p = 0.08), but little association with poor balance, 19 years later. Coefficients in Boyd Orr were in the same direction as ...
Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH-IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL), greatly reduced IGF-I levels (9.0 ng/mL; reference: 180-780 ng/mL), slightly reduced IGF-II levels (197 ng/mL; reference: 267-616 ng/mL) and an elevated IGF-II/IGF-I ...
Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH-IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL), greatly reduced IGF-I levels (9.0 ng/mL; reference: 180-780 ng/mL), slightly reduced IGF-II levels (197 ng/mL; reference: 267-616 ng/mL) and an elevated IGF-II/IGF-I ...
TY - JOUR. T1 - Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas. AU - Atkin, Stephen. AU - Landolt, A. M.. AU - Jeffreys, R. V.. AU - Hipkin, L.. AU - Radcliffe, J.. AU - Squire, C. R.. AU - White, M. C.. PY - 1993. Y1 - 1993. N2 - The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P , 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors ...
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