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insulin-like growth factor receptor

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https://www.readbyqxmd.com/read/29924942/deficient-neurotrophic-factors-of-cspg4-type-neural-cell-exosomes-in-alzheimer-disease
#1
Edward J Goetzl, Carlos Nogueras-Ortiz, Maja Mustapic, Roger J Mullins, Erin L Abner, Janice B Schwartz, Dimitrios Kapogiannis
Exosomes derived from chondroitin sulfate proteoglycan (CSPG) 4 type neural precursor cells (CSPG4Es) were purified from human plasma by sequential immunoabsorption with anti-CSPG4 and anti-platelet growth factor receptor α mAb to characterize the potential in vivo roles of CSPG4 cells in neuronal repair. Hepatocyte growth factor, fibroblast growth factors (FGFs)-2 and -13, and type 1 insulin-like growth factor (IGF-1), which enhance neuronal survival and functions, were quantified in CSPG4E extracts. For CSPG4Es of 24 healthy control subjects, mean levels of hepatocyte growth factor, FGF-13, and IGF-1, but not FGF-2, were significantly higher by up to 7-fold than in their neuronal-derived exosomes, and mean levels of all 4 growth factors were significantly higher by up to 8-fold than in their astrocyte-derived exosomes...
June 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29922232/the-role-of-the-insulin-like-growth-factor-1-pathway-in-immune-tumor-microenvironment-and-its-clinical-ramifications-in-gynecologic-malignancies
#2
Muna Alemi Yahya, Shilhav Meisel Sharon, Shay Hantisteanu, Mordechai Hallak, Ilan Bruchim
Treatment of patients with gynecologic malignancies diagnosed at advanced stages remains a therapeutic challenge. Survival rates of these patients remain significantly low, despite surgery and chemotherapy. Advances in understanding the role of the immune system in the pathogenesis of cancer have led to the rapid evolution of immunotherapeutic approaches. Immunotherapeutic strategies, including targeting specific immune checkpoints, as well as dendritic cell (DC) immunotherapy are being investigated in several malignancies, including gynecological cancers...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29921922/late-life-targeting-of-the-igf-1-receptor-improves-healthspan-and-lifespan-in-female-mice
#3
Kai Mao, Gabriela Farias Quipildor, Tahmineh Tabrizian, Ardijana Novaj, Fangxia Guan, Ryan O Walters, Fabien Delahaye, Gene B Hubbard, Yuji Ikeno, Keisuke Ejima, Peng Li, David B Allison, Hossein Salimi-Moosavi, Pedro J Beltran, Pinchas Cohen, Nir Barzilai, Derek M Huffman
Diminished growth factor signaling improves longevity in laboratory models, while a reduction in the somatotropic axis is favorably linked to human aging and longevity. Given the conserved role of this pathway on lifespan, therapeutic strategies, such as insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibodies (mAb), represent a promising translational tool to target human aging. To this end, we performed a preclinical study in 18-mo-old male and female mice treated with vehicle or an IGF-1R mAb (L2-Cmu, Amgen Inc), and determined effects on aging outcomes...
June 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29917206/up-regulation-of-microrna-503-by-high-glucose-reduces-the-migration-and-proliferation-but-promotes-the-apoptosis-of-human-umbilical-vein-endothelial-cells-by-inhibiting-the-expression-of-insulin-like-growth-factor-1-receptor
#4
L-J Hou, J-J Han, Y Liu
OBJECTIVE: The present study is aimed to investigate the regulatory effect of microRNA (miRNA or miR)-503 on endothelial functions, as well as the mechanism by which high glucose leads to injury of endothelial cells. MATERIALS AND METHODS: When reaching 80% confluency, human umbilical vein endothelial cells (HUVECs) were subjected to non-serum synchronization for 12 h, and medium of cells in high-glucose (HG) group was replaced by normal medium supplemented with 25 mmol/L D-glucose...
June 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29910690/a-dual-specific-igf-i-ii-human-engineered-antibody-domain-inhibits-igf-signaling-in-breast-cancer-cells
#5
Zhizhen Chen, Jie Liu, Dafeng Chu, Yaming Shan, Guixing Ma, Hongmin Zhang, Xiaohua Douglas Zhang, Pu Wang, Qiang Chen, Chuxia Deng, Weizao Chen, Dimiter S Dimitrov, Qi Zhao
The insulin-like growth factors (IGFs), IGF-I and IGF-II, are essential for regulating cell growth, differentiation and metastasis of a broad range of malignancies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Here, we have firstly identified a human engineered antibody domain (eAd) from a phage-displayed VH library. The eAd suppressed the signal transduction of IGF-1R mediated by exogenous IGF-I or IGF-II in breast cancer cell lines through neutralizing both IGF-I and IGF-II...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29910644/overcoming-endocrine-resistance-in-hormone-receptor-positive-breast-cancer
#6
REVIEW
A AlFakeeh, C Brezden-Masley
Endocrine therapy, a major modality in the treatment of hormone receptor (hr)-positive breast cancer (bca), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in bca is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)-targeted therapy. The resistance pathways involve extensive cross-talk between er and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2 (her2), and insulin-like growth factor 1 receptor] and their downstream signalling pathways-most notably pi3k/akt/mtor and mapk...
June 2018: Current Oncology
https://www.readbyqxmd.com/read/29909907/randomized-phase-ii-trial-of-cixutumumab-alone-or-with-cetuximab-for-refractory-recurrent-metastatic-head-and-neck-squamous-cell-carcinoma
#7
Renata Ferrarotto, William N William, Jennifer E Tseng, Shanthi Marur, Dong M Shin, Barbara Murphy, Ezra E W Cohen, Christopher Y Thomas, Richard Willey, Jan Cosaert, Nusrat Harun, J Jack Lee, Ignacio W Wistuba, Robert I Haddad, Bonnie S Glisson
OBJECTIVES: Cixutumumab (CIX) and cetuximab (CET) monoclonal antibodies block ligand-binding to insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) respectively. The objective of this study was to assess the efficacy of CIX alone or combined with CET in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. METHODS: In this open-label phase II trial, 91 R/M HNSCC patients who progressed within 90 days of platinum-based chemotherapy, were randomized to CIX 10 mg/kg alone or with CET 500 mg/m2 every 2 weeks...
July 2018: Oral Oncology
https://www.readbyqxmd.com/read/29903916/insulin-like-growth-factor-1-receptor-stabilizes-the-etv6-ntrk3-chimeric-oncoprotein-by-blocking-its-kpc1-rnf123-mediated-proteasomal-degradation
#8
Cristina E Tognon, Bo Rafn, Naniye Malli Cetinbas, Takumi Kamura, Genny Trigo, Barak Rotblat, Fumihiko Okumura, Masaki Matsumoto, Christine Chow, Monika Davare, Michael Pollak, Thibault Mayor, Poul H Sorensen
Many oncogenes, including chimeric oncoproteins, require insulin-like growth factor 1 receptor (IGF1R) for promoting cell transformation. The ETS variant 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) (EN) chimeric tyrosine kinase is expressed in mesenchymal, epithelial, and hematopoietic cancers and requires the IGF1R axis for transformation. However, current models of IGF1R-mediated EN activation are lacking mechanistic detail. We demonstrate here that IGF-mediated IGF1R stimulation enhances EN tyrosine phosphorylation and that blocking IGF1R activity or decreasing protein levels of the adaptor protein insulin receptor substrate 1/2 (IRS1/2) results in rapid EN degradation...
June 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29901181/microrna%C3%A2-539-inhibits-cell-proliferation-colony-formation-and-invasion-in-pancreatic-ductal-adenocarcinoma-by-directly-targeting-igf%C3%A2-1r
#9
Yongquan Lin, Lihua Rong, Jingrong Zhao, Ronghui Lin, Shuhua Li
MicroRNAs (miRNAs) possess oncogenic and tumour‑suppressive roles in the carcinogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) by regulating the expression of numerous cancer‑related genes. Thus, the investigation on the expression and roles of miRNAs in PDAC may facilitate the identification of novel and effective targets for the clinical diagnosis and treatment of patients with PDAC. miRNA‑539 (miR‑539) has been studied in multiple types of human cancer. However, its expression and potential biological function in PDAC remain unclear...
May 31, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29899203/effects-of-dietary-daidzein-supplementation-on-reproductive-performance-serum-hormones-and-reproductive-related-genes-in-rats
#10
Qiqi Zhang, Daiwen Chen, Bing Yu, Xiangbing Mao, Zhiqing Huang, Jie Yu, Junqiu Luo, Ping Zheng, Yuheng Luo, Jun He
The aim of this study was to investigate the effect of dietary daidzein supplementation on reproductive performance in rats. A total of twenty-four female Sprague⁻Dawley (SD) rats were randomly allocated to two groups and fed either with a basal diet (CON) or basal diet containing 50 mg/kg daidzein (DAI) from gestation until delivery stage. The results show that daidzein supplementation significantly increased the total litter weight and the total viable newborn weight ( p < 0.05). Interestingly, daidzein supplementation acutely elevated the concentrations of serum estrogen, progesterone and insulin-like growth factor-1 ( p < 0...
June 14, 2018: Nutrients
https://www.readbyqxmd.com/read/29898582/decreased-il-1ra-and-ncam-1-cd56-serum-levels-in-unmedicated-patients-with-schizophrenia-before-and-after-antipsychotic-treatment
#11
Che-Sheng Chu, Dian-Jeng Li, Chin-Liang Chu, Chih-Ching Wu, Ti Lu
Objective: Schizophrenia (SZ) has been associated with the inflammatory-related and immunological pathogenesis. This study investigates the aberration of cytokines in patients with SZ. Methods: Thirty patients with SZ without antipsychotic treatment for at least two weeks participated. We measured the serum levels of fourteen cytokines at hospital admission and after 8-week antipsychotic treatment. Severity was measured by expanded version of 24-items brief psychiatric rating scale (BPRS-E)...
June 15, 2018: Psychiatry Investigation
https://www.readbyqxmd.com/read/29895971/%C3%AE-catenin-tcf-activity-regulates-igf-1r-tyrosine-kinase-inhibitor-sensitivity-in-colon-cancer
#12
Hani Lee, Nayoung Kim, Young Ji Yoo, Hyejin Kim, Euna Jeong, SeokGyeong Choi, Sung Un Moon, Seung Hyun Oh, Gordon B Mills, Sukjoon Yoon, Woo-Young Kim
The availability of large-scale drug screening data on cell line panels provides a unique opportunity to identify predictive biomarkers for targeted drug efficacy. Analysis of diverse drug data on ~990 cancer cell lines revealed enhanced sensitivity of insulin-like growth factor 1 receptor/ Insulin Receptor (IGF-1R/IR) tyrosine kinase inhibitors (TKIs) in colon cancer cells. Interestingly, β-catenin/TCF(T cell factor)-responsive promoter activity exhibited a significant positive association with IGF-1R/IR TKI response, while the mutational status of direct upstream genes, such as CTNNB1 and APC, was not significantly associated with the response...
June 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29895074/relation-of-rankl-and-opg-levels-with-bone-resorption-in-patients-with-acromegaly-and-prolactinoma
#13
Firuzan Firat Ozer, Selcuk Dagdelen, Tomris Erbas
The objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured...
June 12, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29891843/establishment-of-a-novel-mouse-xenograft-model-of-human-uterine-leiomyoma
#14
Yusuke Suzuki, Masaaki Ii, Takashi Saito, Yoshito Terai, Yasuhiko Tabata, Masahide Ohmichi, Michio Asahi
Uterine leiomyoma is the most common benign tumour in women, and an appropriate animal model for leiomyoma would be useful for exploring new therapeutic strategies. Therefore, we have been challenged to develop a new simple mouse model for human leiomyoma. Leiomyoma tissues were harvested from myomas resected by different surgical procedures with or without gonadotropin-releasing hormone agonist (GnRHa) treatment and were subcutaneously implanted into BALB/c nude mice with an estradiol/progesterone-releasing pellet...
June 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29888542/reconstructed-evolution-of-insulin-receptors-in-insects-reveals-duplications-in-early-insects-and-cockroaches
#15
Lukas Peter Maria Kremer, Judith Korb, Erich Bornberg-Bauer
Social insects show an extreme degree of phenotypic plasticity. In highly eusocial species, this manifests in the generation of distinct castes with extreme differences in both morphology and life span. The molecular basis of these differences is highly entangled and not fully understood, but several recent studies demonstrated that insulin/insulin-like growth factor signaling (IIS) is one of the key pathways. Here, we investigate the molecular evolution of insect insulin receptors (InRs), which are membrane-bound dimers that enable IIS by relaying extracellular signals to intracellular signaling cascades...
June 10, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/29887522/relaxin-family-member-insulin-like-peptide-6-ameliorates-cardiac-fibrosis-and-prevents-cardiac-remodeling-in-murine-heart-failure-models
#16
Sonomi Maruyama, Chia-Ling Wu, Sumiko Yoshida, Dongying Zhang, Pei-Hsuan Li, Fangzhou Wu, Jennifer Parker Duffen, Rouan Yao, Blake Jardin, Ibrahim M Adham, Ronald Law, Joel Berger, Richard Di Marchi, Kenneth Walsh
BACKGROUND: The insulin/insulin-like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin-like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods. METHODS AND RESULTS: Insl6-deficient and wild-type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks...
June 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29882709/relaxin-receptor-deficiency-promotes-vascular-inflammation-and-impairs-outward-remodeling-in-arteriovenous-fistulas
#17
Taisiya Bezhaeva, Margreet R de Vries, Wouter J Geelhoed, Eric P van der Veer, Sabine Versteeg, Carla M A van Alem, Bram M Voorzaat, Niels Eijkelkamp, Koen E van der Bogt, Alexander I Agoulnik, Anton-Jan van Zonneveld, Paul H A Quax, Joris I Rotmans
The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation...
June 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29882416/role-of-insulin-like-growth-factor-1-receptor-signaling-in-stem-cell-stemness-and-therapeutic-efficacy
#18
Chiao-Fang Teng, Long-Bin Jeng, Woei-Cherng Shyu
Evidence has emerged that stem cells represent a promising therapeutic tool for tissue engineering and regenerative medicine. Thus, identifying functional markers for selecting stem cells capable of superior self-renewal and pluripotency (or multipotency) and maintaining stem cell identity under appropriate culture conditions are critical for guiding the use of stem cells toward clinical applications. Many investigations have implicated the insulin-like growth factor 1 receptor (IGF1R) signaling in maintenance of stem cell characteristics and enhancement of stem cell therapy efficacy...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29881824/inhibition-of-insulin-like-growth-factor-1-receptor-enhances-the-efficacy-of-sorafenib-in-inhibiting-hepatocellular-carcinoma-cell-growth-and-survival
#19
Fang Wang, Thomas Bank, Gregory Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J Cotler, Mitchell F Denning, Michael I Nishimura, Peter Breslin, Wei Qiu
Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer-related death worldwide. The first-line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine-protein kinase c-Raf, serine/threonine-protein kinase B-Raf, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits...
June 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29867764/the-impact-of-initial-energy-reserves-on-growth-hormone-resistance-and-plasma-growth-hormone-binding-protein-levels-in-rainbow-trout-under-feeding-and-fasting-conditions
#20
Björn Thrandur Björnsson, Ingibjörg Eir Einarsdóttir, Marcus Johansson, Ningping Gong
The growth hormone (GH)-insulin-like growth factor I (IGF-I) system regulates important physiological functions in salmonid fish, including hydromineral balance, growth, and metabolism. While major research efforts have been directed toward this complex endocrine system, understanding of some key aspects is lacking. The aim was to provide new insights into GH resistance and growth hormone-binding proteins (GHBPs). Fish frequently respond to catabolic conditions with elevated GH and depressed IGF-I plasma levels, a condition of acquired GH resistance...
2018: Frontiers in Endocrinology
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