Search results for "IGF"
showing 10 items of 68 documents
Contribución de IGF-I en la hiperplasia mamaria promovida por AIB1
2015
El oncogén AIB1 (Amplified in Breast Cancer 1) es un coactivador de la transcripción de genes implicados en la respuesta fisiológica a hormonas y factores de crecimiento. La sobreexpresión de AIB1 es una característica frecuente en muchos tipos de cáncer, incluyendo el de mama. Diferentes estudios con líneas celulares y modelos animales han demostrado que AIB1 interacciona con la ruta de señalización de IGF-I/PI3K/AKT a diferentes niveles moleculares. Por otra parte, la señalización mediada por IGF-I a través de su receptor IGF-IR juega un papel muy importante en el desarrollo de la glándula mamaria y en los procesos patológicos que ocurren en este tejido. Debido a esto, existen múltiples i…
SHIP2: A “NEW” Insulin Pathway Target for Aging Research
2014
Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer's disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment…
Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical…
2014
Abstract Purpose: Mammalian target of rapamycin (mTOR) inhibition activates compensatory insulin–like growth factor receptor (IGFR) signaling. We evaluated the ridaforolimus (mTOR inhibitor) and dalotuzumab (anti-IGF1R antibody) combination. Experimental Design: In vitro and in vivo models, and a phase I study in which patients with advanced cancer received ridaforolimus (10–40 mg/day every day × 5/week) and dalotuzumab (10 mg/kg/week or 7.5 mg/kg/every other week) were explored. Results: Preclinical studies demonstrated enhanced pathway inhibition with ridaforolimus and dalotuzumab. With 87 patients treated in the phase I study, main dose-limiting toxicities (DLT) of the combination were p…
Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis
2022
The association between IGF-1 levels and mortality in humans is complex with low levels being associated with both low and high mortality. The present meta-analysis investigates this complex relationship between IGF-1 and all-cause mortality in prospective cohort studies. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library up to September 2019. Published studies were eligible for the meta-analysis if they had a prospective cohort design, a hazard ratio (HR) and 95% confidence interval (CI) for two or more categories of IGF-1 and were conducted among adults. A random-effects model with a restricted maximum likelihood heterogeneity variance estimator w…
IGF-I, IgA, and IgG responses to bovine colostrum supplementation during training.
2002
This study examined the effect of bovine colostrum (Dynamic colostrum) supplementation on blood and saliva variables ( study 1) and the absorption of orally administered human recombinant insulin-like growth factor (IGF)-I (rhIGF-I) labeled with 123I (123I-rhIGF-I) ( study 2). In study 1, adult male and female athletes were randomly assigned in a double-blind fashion to either an experimental (Dynamic; n = 19) or a control (Placebo; n = 11) group. The former consumed daily 20 g of Dynamic supplement, and the latter 20 g of maltodextrin during a 2-wk training period. After bovine colostrum supplementation, significant increases were noticed in serum IGF-I ( P < 0.01) and saliva IgA ( P &…
Expression and prognostic significance of insulin‑like growth factor-2 receptor in human hepatocellular carcinoma and the influence of transarterial …
2019
Hepatocellular carcinoma (HCC) is one of the most common human malignancies, the incidence of which is growing worldwide. The prognosis of HCC is very poor and it is often accompanied by a high rate of recurrence. Conventional chemotherapeutic approaches are largely inefficient. In order to develop novel effective methods for the early detection and prognosis of HCC, novel markers and therapeutic targets are urgently required. The present study focused on the effects of the expression of the tumor suppressor gene insulin‑like growth factor‑2 receptor (IGF2R) on patient survival and tumor recurrence in patients with HCC; this study paid specific attention to the influence of transarterial ch…
Growth hormone replacement in adults:Real-world data from two large studies in US and Europe
2020
Objective: This report describes the effectiveness and safety of growth hormone replacement in 3180 adult patients with growth hormone deficiency followed-up for 0.0–12.2 years in two completed, complementary, non-interventional, multicentre studies, NordiNet® International Outcome Study (IOS) (NCT00960128) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program (NCT01009905). Design: In both studies, Norditropin® (somatropin; Novo Nordisk A/S, Denmark) was administered at the discretion of the treating physician and according to routine practice. We present data on baseline characteristics, growth hormone dose, safety data and change from baseline in waist circumferenc…
Microdialysis-Assessed Exercised Muscle Reveals Localized and Differential IGFBP Responses to Unilateral Stretch Shortening Cycle Exercise
2020
Microdialysis allows for a preview into local muscle metabolism and can provide physiological insight that blood measurements cannot. Purpose: To examine the potential differential IGF-I system regulation in interstitial fluid during unilateral stretch shortening cycle exercise. Methods: 10 men (26 ± 7 year) performed unilateral jumping [stretch shortening cycle (SSC) exercise at 50% of optimal jump height] until volitional fatigue on a sled apparatus. Biological sampling took place using a catheter inserted into an antecubital vein (serum), and 100 kDa microdialysis probes inserted into the thigh muscle of each exercise/control leg (dialysate). Serum was drawn before (Pre; −3 h) and after …
A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in p…
2011
Abstract Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose. Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis…
Teprotumumab for Thyroid-Associated Ophthalmopathy
2017
Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy.We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to r…