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Igf2 AND insulin

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https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#1
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28727687/hippocampus-dependent-memory-and-allele-specific-gene-expression-in-adult-offspring-of-alcohol-consuming-dams-after-neonatal-treatment-with-thyroxin-or-metformin
#2
E Tunc-Ozcan, S L Wert, P H Lim, A Ferreira, E E Redei
Fetal alcohol spectrum disorder (FASD), the result of fetal alcohol exposure (FAE), affects 2-11% of children worldwide, with no effective treatments. Hippocampus-based learning and memory deficits are key symptoms of FASD. Our previous studies show hypothyroxinemia and hyperglycemia of the alcohol-consuming pregnant rat, which likely affects fetal neurodevelopment. We administered vehicle, thyroxine (T4) or metformin to neonatal rats post FAE and rats were tested in the hippocampus-dependent contextual fear-conditioning paradigm in adulthood...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28716948/cooperative-repression-of-igf2r-translation-by-mir-195-and-rna-binding-protein-cugbp1
#3
Yuan Zhang, Yun Zhang, Lan Xiao, Ting-Xi Yu, Jun-Zhe Li, Jaladanki N Rao, Douglas J Turner, Myriam Gorospe, Jian-Ying Wang
Insulin-like growth factor type-2 (IGF2) receptor (IGF2R) recognizes mannose 6-phosphate-containing molecules and IGF2 and plays an important role in many pathophysiological processes including gut mucosal adaptation. However, the mechanisms that control cellular IGF2R abundance are poorly known. MicroRNAs (miRNAs) and RNA-binding proteins (RBP) critically regulate gene expression programs in mammalian cells by modulating the stability and translation of target mRNAs. Here we report that miRNA-195 (miR-195) and the RBP CUG-binding protein 1 (CUGBP1) jointly regulate IGF2R expression at the posttranscriptional level in intestinal epithelial cells...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28672049/diagnostic-and-prognostic-role-of-sf1-igf2-ki67-p53-adiponectin-and-leptin-receptors-in-human-adrenal-cortical-tumors
#4
Anna Babińska, Rafał Pęksa, Piotr Wiśniewski, Renata Świątkowska-Stodulska, Krzysztof Sworczak
BACKGROUND: The authors have examined the immunohistochemical expression of several proteins and their relationship with adrenal cortical carcinoma (ACC) diagnosis and progression. MATERIALS AND METHODS: A total of 83 patients with benign and malignant adrenal cortex tumors operated on in a single center were included in the study. Expression of the following proteins was examined: steroidogenic factor 1 (SF1), insulin growth factor 2 (IGF2), Ki67, p53, as well as adiponectin (Adipo R1, Adipo R2), and leptin (Ob-R) receptors...
July 3, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28664165/clearance-of-heparan-sulfate-and-attenuation-of-cns-pathology-by-intracerebroventricular-bmn-250-in-sanfilippo-type-b-mice
#5
Mika Aoyagi-Scharber, Danielle Crippen-Harmon, Roger Lawrence, Jon Vincelette, Gouri Yogalingam, Heather Prill, Bryan K Yip, Brian Baridon, Catherine Vitelli, Amanda Lee, Olivia Gorostiza, Evan G Adintori, Wesley C Minto, Jeremy L Van Vleet, Bridget Yates, Sara Rigney, Terri M Christianson, Pascale M N Tiger, Melanie J Lo, John Holtzinger, Paul A Fitzpatrick, Jonathan H LeBowitz, Sherry Bullens, Brett E Crawford, Stuart Bunting
Sanfilippo syndrome type B (mucopolysaccharidosis IIIB), caused by inherited deficiency of α-N-acetylglucosaminidase (NAGLU), required for lysosomal degradation of heparan sulfate (HS), is a pediatric neurodegenerative disorder with no approved treatment. Intracerebroventricular (ICV) delivery of a modified recombinant NAGLU, consisting of human NAGLU fused with insulin-like growth factor 2 (IGF2) for enhanced lysosomal targeting, was previously shown to result in marked enzyme uptake and clearance of HS storage in the Naglu(-/-) mouse brain...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28650518/a-simple-in-silico-strategy-identifies-candidate-biomarkers-for-the-diagnosis-of-liver-fibrosis-in-morbidly-obese-subjects
#6
Pablo J Giraudi, Sabrina E Gambaro, Sofia Ornelas Arroyo, Carla M Chackelevicius, Michela Giuricin, Marta Silvestri, Daniele Macor, Lory S Crocé, Deborah Bonazza, Giorgio Soardo, Nicolò de Manzini, Fabrizio Zanconati, Claudio Tiribelli, Silvia Palmisano, Natalia Rosso
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis...
June 26, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28649356/asymmetric-paternal-effect-on-offspring-size-linked-to-parent-of-origin-expression-of-an-insulin-like-growth-factor
#7
Yolitzi Saldivar Lemus, Jean-Philippe Vielle-Calzada, Michael G Ritchie, Constantino Macías Garcia
Sexual reproduction brings together reproductive partners whose long-term interests often differ, raising the possibility of conflict over their reproductive investment. Males that enhance maternal investment in their offspring gain fitness benefits, even if this compromises future reproductive investment by iteroparous females. When the conflict occurs at a genomic level, it may be uncovered by crossing divergent populations, as a mismatch in the coevolved patterns of paternal manipulation and maternal resistance may generate asymmetric embryonic growth...
June 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28634329/long-days-enhance-recognition-memory-and-increase-insulin-like-growth-factor-2-in-the-hippocampus
#8
Adriano Dellapolla, Ian Kloehn, Harshida Pancholi, Ben Callif, David Wertz, Kayla E Rohr, Matthew M Hurley, Kimberly M Baker, Samer Hattar, Marieke R Gilmartin, Jennifer A Evans
Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28570978/inhibition-of-long-noncoding-rna-igf2as-promotes-angiogenesis-in-type-2-diabetes
#9
Zhuo Zhao, Bin Liu, Bo Li, Chunli Song, Hongying Diao, Ziyuan Guo, Zhibo Li, Jichang Zhang
BACKGROUND: In this study, the angiogenic effect of long noncoding RNA (lncRNA), insulin growth factor 2 antisense (IGF2AS) in type 2 diabetes was evaluated. METHODS: Between Wistar rat and Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, mRNA expressions of IGF2AS and IGF2 in myocardial microvascular endothelial (mMVE) cells were compared by qRT-PCR. In GK mMVE cells, IGF2AS was inhibited by siRNA. Its effects on cell proliferation and invasion were evaluated by MTT and wound-healing assays...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28570711/igf1-and-igf2-specificities-to-the-two-insulin-receptor-isoforms-are-determined-by-insulin-receptor-amino-acid-718
#10
Mie Andersen, Dorte Nørgaard-Pedersen, Jakob Brandt, Ingrid Pettersson, Rita Slaaby
METHODS: Alanine scan of insulin receptor (IR)-B exon 11 and site-directed mutagenesis of amino acid 718 in human IR-A and IR-B were performed. Ligand affinities to wild type and mutated receptors were studied by displacement of radioactive insulin in binding assay on secreted soluble midi receptors or solubilized semi-purified full length receptors stably expressed in Baby Hamster Kidney cells. Phosphorylation of IR in response to insulin, IGF1 and IGF2 was measured using ELISA. RESULTS: Insulin, insulin detemir and insulin glargine maximally showed two fold differences in affinity for human IR-A and IR-B, but IGF1 and IGF2 had up to 10 fold preference for IR-A...
2017: PloS One
https://www.readbyqxmd.com/read/28568977/reproductive-performance-and-expression-of-imprinted-genes-in-somatic-cell-cloned-boars
#11
Tatsuo Kawarasaki, Satoko Enya, Masayoshi Otake, Masatoshi Shibata, Satoshi Mikawa
To assess the performance of boars derived by somatic cell cloning, we analyzed various aspects of their reproductive characteristics and the expression of two imprinted genes. Cloned boars (cloned Duroc × Jinhua) were analyzed for birth weight, growth rate, age at first ejaculation, semen characteristics and fertility, in comparison with naturally bred control boars of the same strain. The expression of imprinted genes was analyzed using the microsatellite marker SWC9 for the paternally expressed gene insulin-like growth factor -2 (IGF2) and with single nucleotide polymorphisms (SNPs) for the gene maternally expressed 3 (MEG3)...
June 1, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28567293/pro-igf2-induced-hypoglycaemia-associated-with-hepatocellular-carcinoma
#12
S A A van den Berg, C G Krol
We present a patient (87 years, female) who was admitted to the emergency department because of loss of consciousness. Previous medical history included advanced-stage hepatocellular carcinoma and associated weight loss. She was found on the ground in an unresponsive state by her daughter and was determined to be hypoglycaemic. Upon bolus administration of 100 mL intravenous glucose (10%), glucose levels increased to 2.9 mmol/L and the patient regained full consciousness. She was admitted to the hospital for further examination, and treatment and continuous intravenous glucose infusion was initiated...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#13
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533070/maternal-and-paternal-periconceptional-nutrition-as-an-indicator-of-offspring-metabolic-syndrome-risk-in-later-life-through-epigenetic-imprinting-a-systematic-review
#14
REVIEW
Ashley R Dunford, Janice M Sangster
AIMS: This review examined whether maternal and paternal periconceptional nutrition effects an offspring's likelihood of developing chronic metabolic related conditions due to epigenetic imprinting. METHODS: A literature search was conducted in multiple science databases and limited to studies published after 2012, in English language and peer reviewed. The data from selected articles were extracted and a qualitative approach was employed due to heterogeneity of results...
May 10, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28522536/a-placental-growth-factor-is-silenced-in-mouse-embryos-by-the-zinc-finger-protein-zfp568
#15
Peng Yang, Yixuan Wang, Don Hoang, Matthew Tinkham, Anamika Patel, Ming-An Sun, Gernot Wolf, Mairead Baker, Huan-Chieh Chien, Kuan-Yu Nick Lai, Xiaodong Cheng, Che-Kun James Shen, Todd S Macfarlan
Insulin-like growth factor 2 (IGF2) is the major fetal growth hormone in mammals. We identify zinc finger protein 568 (ZFP568), a member of the rapidly evolving Kruppel-associated box-zinc finger protein (KRAB-ZFP) family linked primarily to silencing of endogenous retroelements, as a direct repressor of a placental-specific Igf2 transcript (designated Igf2-P0) in mice. Loss of Zfp568, which causes gastrulation failure, or mutation of the ZFP568-binding site at the Igf2-P0 promoter causes inappropriate Igf2-P0 activation...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28521298/insulin-like-growth-factor-2-axis-supports-the-serum-independent-growth-of-malignant-rhabdoid-tumor-and-is-activated-by-microenvironment-stress
#16
Ting Li, Jin Wang, Pengfei Liu, Jiadong Chi, Han Yan, Lei Lei, Zexing Li, Bing Yang, Xi Wang
Malignant rhabdoid tumors (MRTs) are rare, lethal, pediatric tumors predominantly found in the kidney, brain and soft tissues. MRTs are driven by loss of tumor suppressor SNF5/INI1/SMARCB1/BAF47. The prognosis of MRT is poor using currently available treatments, so new treatment targets need to be identified to expand treatment options for patients experiencing chemotherapy resistance. The growth hormone insulin-like growth factor 2 (IGF2) signaling pathway is a promising target to overcome drug resistance in many cancers...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484844/urinary-transcript-quantitation-of-ck20-and-igf2-for-the-non-invasive-bladder-cancer-detection
#17
Karsten Salomo, Doreen Huebner, Manja U Boehme, Alexander Herr, Werner Brabetz, Ulrike Heberling, Oliver W Hakenberg, Daniela Jahn, Marc-Oliver Grimm, Daniel Steinbach, Marcus Horstmann, Michael Froehner, Manfred P Wirth, Susanne Fuessel
PURPOSE: Cytokeratin 20 (CK20) and insulin-like growth factor 2 (IGF2) were previously proposed to be elevated in clinical samples from patients with bladder cancer (BCa). A two cohort design validation study was used to assess the relevance for BCa detection by transcript quantitation of both markers in urine samples. Their diagnostic value was assessed in comparison with voided urine cytology (VUC). METHODS: RNA isolation was carried out using cellular sediments of urine samples from 196/103 histologically positive BCa patients, as well as 97/50 control subjects for the test (TC) and validation cohort (VC), respectively...
May 8, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#18
Maria Schindler, Mareike Pendzialek, Katarzyna Joanna Grybel, Tom Seeling, Jacqueline Gürke, Bernd Fischer, Anne Navarrete Santos
STUDY QUESTION: How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts? SUMMARY ANSWER: In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover. WHAT IS KNOWN ALREADY: Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available...
May 4, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28471495/prognostic-implication-and-functional-role-of-long-noncoding-rna-igf2as-in-human-non-small-cell-lung-cancer
#19
Xin Zhang, Xiujuan Zhang, Rongpeng Hu, Lanxiang Hao
PURPOSE: Emerging evidence shows that long noncoding RNAs (lncRNAs) play important roles in human cancer. In this work, we examined the expression, prognostic implication and functional mechanisms of a lncRNA, insulin growth factor 2 antisense (IGF2AS) in non-small cell lung cancer (NSCLC). METHODS: IGF2AS gene expression was examined by qPCR in both in situ NSCLC clinical samples and in vitro NSCLC cell lines. In patients with NSCLC, postoperative overall survival was estimated according to endogenous IGF2AS expression in their cancerous lung tissues...
May 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28468839/human-relaxins-rlnh1-rlnh2-their-receptor-rxfp1-and-fetoplacental-growth
#20
Kelly Yamasato, Pai-Jong Stacy Tsai, James Davis, Sandra Y Yamamoto, Gillian D Bryant-Greenwood
Relaxin, a systemic and placental hormone, has potential roles in fetoplacental growth. Human placenta expresses two RLN genes, RLNH1 and RLNH2 Maternal obesity is common and is associated with abnormal fetal growth. Our aims were to relate systemic and cord blood RLNH2, placental RLNs and their receptor (RXFP1) with fetoplacental growth in context of maternal body mass index, and associations with insulin-like growth factor 2 (IGF2) and vascular endothelial growth factor A (VEGFA) in the same placentas. Systemic, cord blood and placental samples were collected prior to term labor, divided by prepregnancy body mass index: underweight/normal (N = 25) and overweight/obese (N = 44)...
July 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
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