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insulin-like growth factor receptor

Duthika M Mallawaaratchy, Susannah Hallal, Ben Russell, Linda Ly, Saeideh Ebrahimkhani, Heng Wei, Richard I Christopherson, Michael E Buckland, Kimberley L Kaufman
Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://microvesicles...
October 21, 2016: Journal of Neuro-oncology
C Tsentidis, D Gourgiotis, L Kossiva, A Marmarinos, A Doulgeraki, K Karavanaki
: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D)...
October 20, 2016: Osteoporosis International
Kwong-Fai Wong, Angela M Liu, Wanjin Hong, Zhi Xu, John M Luk
The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities...
October 19, 2016: Oncotarget
Susan M Farabaugh, Bonita T Chan, Xiaojiang Cui, Robert K Dearth, Adrian V Lee
BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer...
October 21, 2016: Cell Communication and Signaling: CCS
Marc A Becker, Xiaonan Hou, Piyawan Tienchaianada, Brian B Haines, Sean C Harrington, S John Weroha, Sriram Sathyanarayanan, Paul Haluska
BACKGROUND: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years...
October 20, 2016: BMC Cancer
Tetsuo Mitsui, Maho Ishida, Michi Izawa, Jun Arita
Estrogen binds to nuclear estrogen receptors (ERs) to modulate transcription of target genes in estrogen-responsive cells. However, recent studies have shown that estrogen also binds to cytoplasmic membrane ERs to modulate protein kinase signaling cascades, leading to non-genomic actions. We investigated whether either nuclear or membrane ERs, including G protein-coupled estrogen receptor 1 (Gper1), mediate the inhibitory action of estrogen on insulin-like growth factor-1 (IGF-1)-induced proliferation of pituitary lactotrophs in primary culture...
October 19, 2016: Endocrine Journal
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
October 18, 2016: Cell Cycle
Abdullah Alzaid, Samuel A M Martin, Daniel J Macqueen
The insulin-like growth factor (IGF) receptor (IGF-IR) is necessary for IGF signalling and has essential roles in cellular growth. In teleost fish, two distinct IGF-IR duplicates are conserved called IGF-IRa and IGF-IRb. However, while a salmonid-specific whole genome duplication (ssWGD) is known to have expanded several key genes within the IGF axis, its impact on the IGF-IR repertoire remains unresolved. Using bioinformatic and phylogenetic approaches, we establish that salmonids retain two IGF-IRa paralogues from ssWGD and a single IGF-IRb copy...
October 17, 2016: Scientific Reports
J L Chen, P Zheng, C Zhang, B Yu, J He, J Yu, J Q Luo, X B Mao, Z Q Huang, D W Chen
This study was conducted to investigate the effects of benzoic acid (BA) on growth performance, intestinal development and intestinal barrier function in weaned pigs. Ninety weaned pigs were randomly assigned to one of three treatments: a basal diet (CON), the basal diet supplemented with 2000 mg/kg benzoic acid (BA1) and 5000 mg/kg benzoic acid (BA2). At the end of days 14 and 42, six pigs per treatment were randomly selected to collect plasma and intestinal samples. Results showed that BA supplementation not only improved final body weight, daily growth and feed conversion ratio from days 15 to 42 and days 1 to 42, but also decreased the activity of plasma diamine oxidase (day 42) and the pH values of jejunal contents (day 14) (p < 0...
October 16, 2016: Journal of Animal Physiology and Animal Nutrition
David S Geller, Jonathan Morris, Ekaterina Revskaya, Mani Kahn, Wendong Zhang, Sajida Piperdi, Amy Park, Pratistha Koirala, Hillary Guzik, Charles Hall, Bang Hoang, Rui Yang, Michael Roth, Jonathan Gill, Richard Gorlick, Ekaterina Dadachova
INTRODUCTION: Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS. METHODS: Binding efficiency of the Rhenium-188((188)Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis...
July 30, 2016: Nuclear Medicine and Biology
Khairy M A Zoheir, Gamaleldin I Harisa, Ahmed A Allam, Ligu Yang, Xiang Li, Aixin Liang, Ahmed A Abd-Rabou, Abdel Halim Harrath
The present study aimed to evaluate the in vitro effect of alpha lipoic acid (ALA) addition to the culture medium on the development of the bovine secondary preantral follicles. Bovine secondary preantral follicles were collected and divided into two groups depending on their size (80-100 μm and 100-110 μm). They were cultured in vitro for 15 days (D) using different media including at three different doses of ALA. The genes expression levels of follicle-stimulating hormone beta-subunit (FSHR), insulin-like growth factor (IGF-1), Activin, luteinizing hormone/choriogonadotropin receptor, bone morphogenetic protein receptor type IA, transforming growth factor beta receptor 1, growth differentiation factor 9, BCL2-associated X protein (BAX), and C-Myc were studied using real-time polymerase chain reaction...
September 13, 2016: Theriogenology
Amelia Entingh-Pearsall, C Ronald Kahn
No abstract text is available yet for this article.
October 14, 2016: Journal of Biological Chemistry
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
Francesco De Francesco, Antonio Graziano, Letizia Trovato, Gabriele Ceccarelli, Maurizio Romano, Marco Marcarelli, Gabriella Maria Casella De Angelis, Umberto Cillo, Michele Riccio, Giuseppe Andrea Ferraro
BACKGROUND: The etiology of non-healing ulcers depends on both systemic and local factors. The introduction of advanced dressing, negative wound therapy and compression therapy have undoubtedly improved clinical outcomes. The principal aim of study was to demonstrate the efficacy of dermal micrografts in the treatment of ulcers with different etiologies. The second aim was to investigate in vitro the action of micrografts in the regenerative process. METHODS: The dermal micro-grafts were obtained from mechanical disaggregation of small pieces of skin tissue through a medical device called Rigeneracons...
October 13, 2016: Stem Cell Reviews
Lu Han, Guo-Feng Zhang, Yue-Hu Cheng, Qi-Cheng Zhao
OBJECTIVE: This study is designed to evaluate the correlations of insulin-like growth factor I (IGF-I) and insulin-like growth factor I receptor (IGF-IR) expressions with the clinicopathological features and prognosis of patients with colon cancer. METHODS: From January 2010 to January 2009, tissue samples were collected from 121 colon cancer patients, 147 with colon adenoma and 63 patients with chronic diarrhea. Real-time quantitative polymerase chain reaction was used to analyze the mRNA expressions of IGF-I and IGF-IR...
October 13, 2016: Japanese Journal of Clinical Oncology
X-Q Zhao, T-J Liang, J-W Fu
OBJECTIVE: The aim of this study was to investigate the target gene of miR-494 and its roles in tumor growth of gastric cancer (GC). PATIENTS AND METHODS: Expression of miR-494 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in gastric cancer tissues and cell lines. Then, luciferase reporter assay was used to elucidate whether insulin-like growth factor 1 receptor (IGF1R) is a target gene of miR-494. Finally, the roles and mechanism of miR-494 in the regulation of tumor invasion were further investigated...
September 2016: European Review for Medical and Pharmacological Sciences
Claire M Perks, H A Zielinska, Jing Wang, Caroline Jarrett, A Frankow, Michael R Ladomery, Amit Bahl, Anthony Rhodes, Jon Oxley, Jeff M P Holly
Men who develop prostate cancer (PCa) increasingly have one of the co-morbidities associated with a Western lifestyle that are characterized by hyperinsulinemia, hyperglycemia and increased expression of insulin-like growth factors-I (IGF-I) and IGF-II. Each have been associated with poor prognosis and more aggressive cancers that exhibit increased metabolism and increased glucose uptake. The insulin receptor (IR) has two splice isoforms IR-A and IR-B: IR-A has a higher affinity for IGF-II comparable to that for insulin, whereas the IR-B isoform predominantly just binds to insulin...
2016: Frontiers in Endocrinology
Emiliano Calvo, Jean-Charles Soria, Wen Wee Ma, Tao Wang, Rastilav Bahleda, Anthony Tolcher, Diana Gernhardt, Joseph O'Connell, Robert Millham, Nagdeep Giri, Michael J Wick, Alex A Adjei, Manuel Hidalgo
PURPOSE: This phase I, open-label, single-arm trial assessed the safety and tolerability of dacomitinib-figitumumab combination therapy in patients with advanced solid tumors. EXPERIMENTAL DESIGN: A standard 3+3 dose escalation/de-escalation design was utilized. Starting doses were figitumumab 20 mg/kg administered intravenously once every 3 weeks (q3w) and dacomitinib 30 mg administered orally once daily. We also performed an independent study of the combination in patient-derived xenograft (avatar mouse) models of adenoid cystic carcinoma (ACC)...
October 12, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Aleksandra M Ochnik, Robert C Baxter
Insulin-like growth factor receptor (IGF1R) signaling as a therapeutic target has been widely studied and clinically tested. Despite the vast amount of literature supporting the biological role of IGF1R in breast cancer, effective clinical translation in targeting its activity as a cancer therapy has not been successful. The intrinsic complexity of cancer cell signaling mediated by many tyrosine kinase growth factor receptors that work together to modulate each other and intracellular downstream mediators in the cell highlights that studying IGF1R expression and activity as a prognostic factor and therapeutic target in isolation is certainly associated with problems...
November 2016: Endocrine-related Cancer
Riia K Junnila, Silvana Duran-Ortiz, Ozan Suer, Elahu G Sustarsic, Darlene E Berryman, Edward O List, John J Kopchick
Growth hormone (GH) and insulin like growth factor I (IGF-I) are important for a variety of physiological processes including growth, development and aging. Mice with reduced levels of GH and IGF-I have been shown to live longer than wild type controls. Our laboratory has previously found that mice with aGHreceptor gene knockout (GHRKO) from conception exhibit low rates of cancer, resistance to diet-induced diabetes, and extension of lifespan. The GHRKO mouse as well as other mouse lines with reduced GH action display low IGF-I levels, smaller body size, increased adiposity and increased longevity...
October 12, 2016: Endocrinology
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