Two types of receptors for insulin-like growth factors (IGFs) were characterized in glioma cell lines established from different human brain tumors of glial origin (astrocytoma grades III and IV) by competitive binding assay, affinity labeling, and protein phosphorylation. Type I IGF receptor is a heterodimer composed of α-subunits (Mr 130,000), which bind IGF I and II with equal affinity, and of β-subunits (Mr 98,000), which show tyrosine kinase activity and autophosphorylation stimulated by IGF I and II with equal potency. The type II IGF binding site is a monomer (Mr 250,000) which binds IGF II with 10 times higher affinity than IGF I. The cellular concentration of type II IGF binding site is about 2- to 5-fold higher than the amount of type I IGF receptor. The characteristics of the two types of IGF receptors in human glioma cell lines are similar to those described recently in fetal rat astrocytes. In contrast the type I IGF receptor in glioma cells is different from that studied ...
The type I insulin-like growth factor (IGF) receptor (IGF1R) is a transmembrane tyrosine kinase involved in breast cancer proliferation, survival, and metastasis. Several monoclonal antibodies directed against the receptor are in clinical trials. In
Domains of the insulin-like growth factor I receptor required for the activation of extracellular signal-regulated kinases.: The type 1 insulin-like growth fact
Semantic Scholar extracted view of Molecular and cellular aspects of the insulin-like growth factor I receptor. by Derek Leroith et al.
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.
Background: - IMC-A12 is an experimental substance designed to inhibit a protein called Type I Insulin-Like Growth Factor Receptor (IGF-1R), whic
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TY - JOUR. T1 - Effect of insulin-like growth factor type 1 on critical-size defects in diabetic rats. AU - Thaller, S. R.. AU - Lee, T. J.. AU - Armstrong, M.. AU - Tesluk, H.. AU - Stern, J. S.. PY - 1995. Y1 - 1995. N2 - A number of investigators have reported on the clinically significant relationship between diabetes mellitus and impaired wound healing. Diabetic patients have an increased frequency of infection, delayed scar formation, and poor bony union. Investigations completed in our laboratory have demonstrated that insulin-like growth factor type 1 (IGF-1), a somatomedin C, has shown promise for accelerating bony repair. The purpose of this study was to examine the effects of recombinant IGF-1 on standardized, critical-size calvarial defects in 25 adult, male streptozocin-induced diabetic rats. From our study, it appears that IGF-1 exerts a potentiating effect on the repair of bony defects in diabetes-induced rats.. AB - A number of investigators have reported on the clinically ...
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 ...
Schmidt B, Kiecke-Siemsen C, Waheed A et al. (1995). "Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor". J. Biol. Chem. 270 (25): 14975-82. PMID 7797478. doi:10.1074/jbc.270.25.14975. CS1 održavanje: Eksplicitna upotreba et al. (link) ...
The mannose 6-phosphate/insulin-like growth factor-II (Man-6-P/IGF-II) receptor is known to cycle between the Golgi, endosomes, and the plasma membrane. In the Golgi the receptor binds newly synthesized lysosomal enzymes and transports them directly to an endosomal (prelysosomal) compartment without traversing the plasma membrane. Deletion of the carboxyl-terminal Leu-Leu-His-Val residues of the 163 amino acid cytoplasmic tail of the bovine Man-6-P/IGF-II receptor partially impaired this function, resulting in the diversion of a portion of the receptor-ligand complexes to the cell surface, where they were endocytosed. The same phenotype was observed when 134 residues of the cytoplasmic tail were deleted from the carboxyl terminus. Disruption of the Tyr24-Lys-Tyr-Ser-Lys-Val29 plasma membrane internalization signal alone had little effect on Golgi sorting, but when combined with either deletion resulted in a complete loss of this function. The mutant receptors retained the ability to recycle to ...
TY - JOUR. T1 - Binding of insulin-like growth factor-I to rat uterus; variations during sensitization and decidualization. AU - Chandrasekhar, Y.. AU - Narayan, S.. AU - Singh, Pomila. AU - Nagamani, M.. PY - 1990. Y1 - 1990. N2 - IGF-I receptors have been identified and characterized in a variety of tissues. In this study receptors for IGF-I in the rat uterine tissue were identified and characterized. We have demonstrated IGF-I receptors in crude uterine membranes by binding and cross-linking experiments. IGF-I binding to the rat uterine membranes displayed time, temperature and pH dependence, and optimal binding conditions were achieved by 20 h of incubation at 4°C, at a pH of 7.8. Uterine IGF-I binding sites were specific for binding IGF-I peptide and demonstrated less than 100 x lower affinity for insulin. The binding was reversible and Scatchard analysis indicated presence of a single class of binding sites with an apparent dissociation constant of 1.68 ± 0.24 nmol/l and B(max) of 0.82 ...
Objective:To determine whether insulinlike growth factor-I (IGF-I) and hepatocyte growth factor (HGF) cooperate to induce migration and invasion of human colorectal carcinoma (CRC) cells and whether the effects of IGF-I and/or HGF are mediated through activation of the urokinase plasminogen activato
mTOR is a central controller for cell growth/proliferation and survival. Recent studies have shown that mTOR also regulates cell adhesion, yet the underlying mechanism is not known. Here we found that inhibition of mTOR by rapamycin reduced the basal or type I insulin-like growth factor (IGF-1)-stimulated adhesion of cancer cells. Further research revealed that both mTORC1 and mTORC2 were involved in the regulation of cell adhesion, as silencing expression of raptor or rictor inhibited cell adhesion.
Human serum and urine contain polypeptides which bind mannose 6-phosphate (M6P) and insulin-like growth factor II (IGF II) and crossreact with antibodies against the M6P/IGF II receptor. These polypeptides are considered to be fragments of the M6P/IGF II receptor. The major Mr approx. 205,000 fragment in serum and urine is about 10 kDa smaller in size than the membrane-associated receptor and is accompanied by minor forms with Mr values ranging from 104,000 to 180,000. The presence of receptor fragments in biological fluids indicates that shedding is one of the mechanisms contributing to the turnover of the M6P/IGF II receptor and that receptor fragments are part of the heterogenous group of serum proteins whic bind IGF II. ...
J:45195 Melnick M, Chen H, Buckley S, Warburton D, Jaskoll T, Insulin-like growth factor II receptor, transforming growth factor-beta, and Cdk4 expression and the developmental epigenetics of mouse palate morphogenesis and dysmorphogenesis. Dev Dyn. 1998 Jan;211(1):11-25 ...
Introduction: Insulin receptor (IR) and type 1 and type 2 insulin-like growth factor receptors (IGF1 R and IGF2R) play important roles in regulation of placental and foetal growth. All three receptors are abundantly glycosylated. N-glycosylation significantly affects protein conformation and may alter its function. We have recently found that the N-glycome of placental membrane proteins alters during gestation. The aim of the study presented herein was to investigate whether there were gestation-related changes in N-glycan profiles of placental IR and IGFRs. Methods: Placentas from healthy women at first (FTP) and third trimester (TTP) of pregnancy were collected, membrane proteins isolated, solubilised and used as the source of IR and IGFRs. Reactivity of glycoforms of IR and IGFRs with lectins was monitored by measuring radioactivity of I-125-ligands-receptors complexes. Results: Significant differences in the binding pattern of all three receptors to the lectins were observed betwee...n FTP ...
The interactions of insulin-like growth factors (IGFs) with the type I IGF receptor are modulated by a family of high-affinity IGF binding proteins (IGFBPs). One of these, IGFBP2, demonstrates a striking spatiotemporal relationship with IGF-I during cerebellar and retinal development. IGF-I mRNA is transiently expressed in large projection neurons--cerebellar Purkinje and retinal ganglion cells--while IGFBP2 mRNA is selectively expressed by contiguous neuroglia--Bergmann glia in the cerebellum and Muller cells and astrocytes of the nerve fiber layer in the retina. IGF-I and IGFBP2 gene expression is not only neuroanatomically coordinated but also temporally synchronized, peaking together during the postnatal maturation of these structures. This pattern of IGF system expression suggests that IGFBP2 is closely related to IGF-Is action in the developing nervous system.. ...
Rotwein P, et al. Genetic analysis of the hypervariable region flanking the human insulin gene. Am. J. Hum. Genet. 39: 291-299, 1986. PubMed: 2876625 Rotwein P, et al. Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. J. Biol. Chem. 261: 4828-4832, 1986. PubMed: 2937782 ...
The insulin-like growth factor type 1 receptor (IGF-1R) is important in tumorigenesis and its overexpression occurs in numerous tumor tissues. To date, therapeutic approaches based on monoclonal antibodies and tyrosine kinase inhibitors targeting IGF-1R have only shown clinical benefit in specific patient populations. We report a unique IGF-1R-targeted antibody-drug conjugate (ADC), W0101, designed to deliver a highly potent cytotoxic auristatin derivative selectively to IGF-1R overexpressing tumor cells. The monoclonal antibody (hz208F2-4) used to prepare the ADC was selected for its specific binding properties to IGF-1R compared to the insulin receptor (IR), and for its internalization properties. Conjugation of a novel auristatin derivative drug linker to hz208F2-4 did not alter its binding and internalization properties. W0101 induced receptor-dependent cell cytotoxicity in vitro when applied to various cell lines overexpressing IGF-1R but it did not affect normal cells. Efficacy studies ...
The cells of the IM-9 human lymphocyte-derived line contain a sub-population of insulin-binding sites whose immunological and hormone-binding characteristics closely resemble those of the atypical insulin-binding sites of human placenta. These binding sites, which have moderately high affinity for multiplication-stimulating activity [MSA, the rat homologue of insulin-like growth factor (IGF) II] and IGF-I, are identified on IM-9 cells by 125I-MSA binding. They account for approximately 30% of the total insulin-receptor population, and do not react with a monoclonal antibody to the type I IGF receptor (alpha IR-3). The relative concentrations of unlabelled insulin, MSA and IGF-I required to displace 50% of 125I-MSA from these binding sites (1:4.7:29 respectively) are maintained for cells, particulate membranes, Triton-solubilized membranes precipitated either by poly(ethylene glycol) or a polyclonal antibody (B-10) to the insulin receptor, and receptors purified by insulin affinity ...
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 ...
Background: Type 1 insulin-like growth factor receptor (IGF-1R) is the product of a single-copy gene located on chromosome 15 and is ubiquitously expressed in humans. Increased hepatic IGF-1R gene expression is found in hepatocellular carcinoma and in chronic hepatitis C, making parenchymal and non-parenchymal cells more susceptible to the mitogenic effects of IGF-1.. Objective and hypotheses: As we have previously demonstrated that IGF-1 and IGF-2 circulating levels are rearranged in relation with the severity of liver damage in obese children with NAFLD, our aim was to investigate the hepatic expression of IGF-1R in the same group of patients.. Method: In this preliminary study, immunohistochemistry and immunofluorescence were applied for analysing the expression of IGF-1R in 12 children with NAFLD. Three liver samples from healthy subjects were used as reference for tissue expression of IGF-1R. Expression data were correlated with severity of disease and with the expression of various liver ...
Insulin-like growth factors (IGFs) interact with specific cell surface receptors to mediate cell growth. Intracellular effects of the IGFs are mediated by activation of secondary messenger molecules. One of these proteins, insulin receptor substrate-1 (IRS-1), is phosphorylated after type I IGF receptor activation and has a major role in IGF signaling. Receptor activation also is influenced by high-affinity IGF binding proteins (IGFBPs). In serum, IGFBP-3 is the predominant species. The role of IGFBP-3 in the regulation of breast cancer cell growth is unclear; both growth inhibition and stimulation have been documented in tissue culture systems. To investigate the influence of IGFBP-3 and IRS-1 in breast cancer, we measured levels of these proteins by ELISA and immunoblotting in 195 node-negative primary human breast cancers and compared their levels with known prognostic factors and disease-free survival (DFS). IGFBP-3 levels correlated positively with tumor size (r = 0.27, P , 0.0001) and ...
Tumor-Induced Hypoglycemia Caused by Excess Production of IGF-II (See also Chap. 339) Mesenchymal tumors, hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor type II (IGF-II) precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin-like actions. The gene encoding IGF-II resides on a chromosome 11p15 locus that is normally imprinted (that is, expression is exclusively from a single parental allele). ...
Polyclonal antibody for IGF I/IGF1 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Human. IGF I/IGF1 information: Molecular Weight: 21841 MW; Subcellular Localization: Secreted.
Sachin Nalin Vyas, PhD, MS, of UNC Urology has been awarded to study the Health Related Quality of Life (HRQOL) among the group of patients undergoing surgical grafting for the correction of Peyronies Diseases at UNC and Tulane University with Professor Wayne Hellstrom, MD, FACS.
The study of dietary intake of vegetables and fruit and lung cancer risk in Harbin, Heilongjiang province, northeast China(b) and Tin Corporation (YTC) miners in Yunnan(c), showed a positive effect of intake of celery daily in reduced risk of lung cancer. According to Dr. Belanger JT. research, Perillyl alcohol, a monoterpene isolated from the essential oils of celery seeds, exhibited the effect of inducing apoptosis in tumor cells without affecting normal cells and reverting tumor cells back to a differentiated state in very cancer cells, including lung cancer, through increased mannose-6-phosphate/insulin-like growth factor II receptors, tissue growth factor beta receptors, Bak and decreased ras protein prenylation, ubiquinone synthesis, and induced Phase I and Phase II detoxification systems(d ...
TY - JOUR. T1 - Distribution and relevance of insulin-like growth factor-I receptor in metanephric development. AU - Liu, Zheng Z.. AU - Wada, Jun. AU - Alvares, Keith. AU - Kumar, Anil. AU - Wallner, Elisabeth I.. AU - Kanwar, Yashpal S.. PY - 1993/12. Y1 - 1993/12. N2 - During embryogenesis, various ligand-receptor interactions take place to modulate the development and growth of various mammalian organs. During these interactions, a critical concentration of a given receptor is needed to elicit a ligand-induced biologic response at a defined gestational stage of the fetus. In this study, the distribution and the relevance of insulin-like growth factor-I receptor (IGF-IR) in metanephric development was investigated. Kidneys were harvested from mouse embryos at days 13 to 19 of fetal gestation, and maintained in a metanephric culture system. Immunofluorescence studies, using anti-IGF-IR, revealed a high expression of IGF-IR at day 13, which declined during the later stages of gestation through ...
Inhibition of epidermal growth factor receptor (EGFR) signaling sensitizes human malignant glioma cells to death ligand-induced apoptosis. However, tumor cells may compensate the loss of EGFR signaling by activation of the type 1 insulin-like growth factor receptor (IGF-1R). We here report that anta …
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
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 ...
Longevity in livestock is a valuable trait. When productive animals live longer, fewer replacement animals need to be raised. However, selection for longevity is not commonly the focus of breeding programs as direct selection for long-lived breeding stock is virtually impossible until late in the reproductive life of the animal. Additionally the underlying genetic factors or genes associated with longevity are either not known, or not well understood. In humans, there is evidence that IGF 1 receptor (IGF1R) is involved in longevity. Polymorphism in the IGF1R gene has been associated with longevity in a number of species. Recently, 3 alleles of ovine IGF1R were identified, but no analysis of the effect of IGF1R variation on sheep longevity has been reported. In this study, associations between ovine IGF1R variation, longevity and fertility were investigated. Polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) was used to type IGF1R variation in 1,716 New Zeal ...
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 ...
Caloric restriction (CR) inhibits tumorigenesis in rodents. To understand the basis for this effect the binding of insulin, insulin-like growth factor I/somatomedin C (IGF-I/Sm-C), insulin-like growth factor II/multiplication stimulating activity (IGF-II/MSA), and epidermal growth factor were examined to membrane preparations of 7,12-dimethylbenz(a)anthracene-induced mammary adenocarcinomas and several normal tissues from female Sprague-Dawley rats. Animals were fed ad libitum (AL) or 25% and 40% calorically restricted diets. Large, palpable (LP) and small, ≤ 100 mg, nonpalpable (SNP) tumors were evaluated. Growth factor binding to tumors was differentially affected by CR. IGF-I/Sm-C binding was comparable for AL-LP, AL-SNP, and 25% CR-LP tumors, but elevated in 25% CR-SNP tumors. Scatchard analysis revealed high and low affinity IGF-I/Sm-C binding sites, with AL-SNP and 25% CR-SNP tumors exhibiting similar levels of high affinity sites and at a greater concentration than AL-LP and 25% CR-LP ...
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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 ...
The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib.. One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry.. IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological ...
In this case-control study conducted in a low-risk population in China, we found a strong dose-dependent association between increasing plasma levels of total IGF-I and prostate cancer risk, as well as inverse associations with levels of IGFBP-1 and IGFBP-3. In contrast, we found no association between levels of IGF-II and prostate cancer risk.. The effects of IGF-I, IGFBP-1, and IGFBP-3 on prostate cancer risk are biologically plausible, as demonstrated by numerous in vitro and in vivo studies (1 , 9) . It has been suggested that total plasma IGF-I may be a surrogate for tissue IGF-I bioactivity (4 , 9) , which is supported by our finding that the prostate cancer risk associated with the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) was similar to that for plasma IGF-I alone. In this manner, increasing levels of circulating IGF-I may indicate increasing activation of the type I IGF receptor and thus increasing growth of prostate cancer. In contrast, increasing levels of ...
Levels of IGF-1 and IGFBP-3 in ESFT patients can identify patients with the most widespread disease. The IGFBP-3 to IGF-1 ratio in patients with either localized or metastatic disease identified patients with a trend toward increased survival. Further prospective evaluation with higher patient numbe …
Loss of Imprinting of Insulin-like Growth Factor-II in Wilms Tumor Commonly Involves Altered Methylation but not Mutations of CTCF or Its Binding ...
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
Cortisol opposes the activity of anabolic hormones, including testosterone, growth hormone, insulinlike growth factor 1 - a.k.a. IGF-1 - and insulin, although, conversely, the same hormones oppose cortisols catabolic activity. One measure of overtraining is the ratio of testosterone to cortisol - if it tips in favour of cortisol, youve slipped into overtraining. Interestingly, however, one study found that cortisol actually encourages greater activity of free - that is, active - testosterone following exercise by stimulating its release from its protein binder in the blood.1 Another recent study showed that intense training increases cortisol by stimulating the enzyme that converts inactive cortisone into active cortisol.2 Yet another found that, contrary to popular belief, low-intensity exercise not only doesnt increase cortisol but actually lowers it.3 ...
Estrogen receptor alpha (ER) and the insulin-like growth factor I receptor (IGF-IR) pathways are engaged in a Ribitol functional cross talk in breast malignancy promoting tumor progression and increased resistance to anticancer treatments and radiotherapy. an increase of ER transcriptional activity suggesting a repressive role of the Forkhead transcription factor in ER function. Moreover 17 […]. ...
Somatomedin definition is - any of several endogenous peptides produced especially in the liver that are dependent on and probably mediate growth hormone activity (as in sulfate uptake by epiphyseal cartilage).
Dávila D, Torres-Aleman I. Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling ...
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 ...
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