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insulin-like growth factor receptor

Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
Takako Kawanami, Tomoko Tanaka, Yuriko Hamaguchi, Takashi Nomiyama, Hajime Nawata, Tosihiko Yanase
We previously identified a novel selective androgen receptor modulator (SARM), S42, which does not stimulate prostate growth but has a beneficial effect on lipid metabolism. In the prostate cancer (PC) cell line LNCaP, S42 did not induce androgen receptor (AR) transactivation but antagonized 5α-dihydrotestosterone (DHT)-induced AR activation. Next, we investigated whether S42 suppresses the growth of PC cell lines. Basal growth of LNCaP cells was significantly suppressed by treatment with S42 compared with vehicle, as determined by cell counting and BrdU assays...
February 12, 2018: Endocrinology
Miles J De Blasio, Stuart A Lanham, Dominique Blache, Richard Oc Oreffo, Abigail L Fowden, Alison J Forhead
Widespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using micro-computed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125-130 days of gestation (term ~145 days), chronically-catheterised singleton sheep fetuses were infused intravenously for five days with either saline (0.9% saline, n=13), recombinant ovine leptin at two doses (0...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Kwan Ho Jeong, Ji Hee Jung, Jung Eun Kim, Hoon Kang
Prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (DP2) is known to be an important factor in androgenetic alopecia (AGA). However, the effect of PGD2 in human dermal papilla cells (hDPCs) is not fully understood. The function of PGD2-induced expression of the androgen receptor (AR), DP2, and AKT (protein kinase B) signal were examined by using real time-PCR (qRT-PCR), western blot analysis, immunocytochemistry (ICC), and siRNA transfection system. PGD2 stimulated AR expression and AKT signaling through DP2...
February 12, 2018: International Journal of Molecular Sciences
Shichao Tong, Jimin Yin, Ji Liu
Platelet-rich plasma (PRP) is autologous and multifunctional. Platelet concentrate from blood contains highly concentrated platelets and various types of cells, including growth factors. PRP promotes the recovery of cell proliferation and differentiation. Osteonecrosis of the femoral head is a disease caused by femoral head damage or an insufficient blood supply, which leads to the death of bone cells and abnormal bone marrow composition. The subsequent repair of bone cells may result in changes to the structure of femoral head, femoral head collapse and joint dysfunction...
February 2018: Experimental and Therapeutic Medicine
Ying Ye, Juhua Zhuang, Guangdong Wang, Saifei He, Suiliang Zhang, Guoyu Wang, Jing Ni, Jiening Wang, Wei Xia
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second-most frequent cause of cancer-associated deaths worldwide. Previously, increasing studies report that microRNAs (miRNAs/miRs) are abnormally expressed in various types of human cancers and may participate in the tumourigenesis and tumour development of HCC. miRNA-based targeted therapy is effective against different molecular targets and may increase the sensitisation of cancer cells to therapy by several folds. Therefore, further validation of potentially important miRNAs involved in HCC initiation and progression may provide valuable insights into the treatment of patients with HCC...
January 2018: Experimental and Therapeutic Medicine
Erika Brolin, Sofia Zelleroth, Anna Jonsson, Mathias Hallberg, Alfhild Grönbladh, Fred Nyberg
The use of opioid analgesics to treat non-cancer pain has increased over the years. Many chronic pain patients suffer from numerous adverse effects, such as reduced quality of life, development of dependence, and cognitive impairments. Cognitive processes are regulated by several systems, one of which involves growth hormone (GH) and its secondary mediator insulin-like growth factor-1 (IGF-1), but also glutamatergic transmission, including receptors such as the N-methyl-d-aspartate (NMDA)-receptor complex. In the laboratory, repeated injections are commonly used to establish animal models of long-term or chronic drug exposure...
February 5, 2018: Pharmacology, Biochemistry, and Behavior
Marie Guerard, Thomas Robin, Pascal Perron, Anne-Sophie Hatat, Laurence David-Boudet, Laetitia Vanwonterghem, Benoit Busser, Jean-Luc Coll, Sylvie Lantuejoul, Beatrice Eymin, Amandine Hurbin, Sylvie Gazzeri
Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xenografts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin...
February 5, 2018: Cancer Letters
Yuyao Wang, Dandan Zhang, Yi Zhang, Ni Ni, Zhimin Tang, Zhisha Bai, Bingqiao Shen, Hao Sun, Ping Gu
Strategies to improve retinal progenitor cell (RPC) capacity to yield proliferative and multipotent pools of cells that can efficiently differentiate into retinal neurons, including photoreceptors, could be vital for cell therapy in retinal degenerative diseases. In this study, we found that insulin-like growth factor-1 (IGF-1) plays a role in the regulation of proliferation and differentiation of RPCs. Our results show that IGF-1 promotes RPC proliferation via IGF-1 receptors (IGF-1Rs), stimulating increased phosphorylation in the PI3K/Akt and MAPK/Erk pathways...
February 8, 2018: Cell Cycle
Alfonso Saera-Vila, Ke'ale W Louie, Cuilee Sha, Ryan M Kelly, Phillip E Kish, Alon Kahana
Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration...
2018: PloS One
Jordan Rowlands, Vinicius Cruzat, Rodrigo Carlessi, Philip Newsholme
Pharmacological long lasting Glucagon-like peptide-1 (GLP-1) analogues, such as Exendin-4, have become widely used diabetes therapies. Chronic GLP-1R stimulation has been linked to β-cell protection and these pro-survival actions of GLP-1 are dependent on the activation of the mammalian target of rapamycin (mTOR) leading to accumulation of Hypoxia inducible factor 1 alpha (HIF-1α). Recent studies from our lab indicate that prolonged GLP-1R stimulation promotes metabolic reprograming of β-cells towards a highly glycolytic phenotype and activation of the mTOR/HIF-1α pathway was required for this action...
February 2018: Peptides
Victor A Gault, Christian Hölscher
Enzyme-resistant receptor agonists of the incretin hormone glucagon-like peptide-1 (GLP-1) have shown positive therapeutic effects in people with type 2 diabetes mellitus (T2DM). T2DM has detrimental effects on brain function and impairment of cognition and memory formation has been described. One of the underlying mechanisms is most likely insulin de-sensitization in the brain, as insulin improves cognitive impairments and enhances learning. Treatment with GLP-1 receptor agonists improves memory formation and impairment of synaptic plasticity observed in animal models of diabetes-obesity...
February 2018: Peptides
A Ajith Kumar, Siva Kumar Nadimpalli
Mannose 6-phosphate/IGF-II receptor mediated lysosomal clearance of insulin like growth factor-II is significantly associated with the evolution of placental mammals. The protein is also referred to as the IGF-II receptor. Earlier studies suggested relatively low binding affinity between the receptor and ligand in prototherian and metatherian mammals. In the present study we cloned the IGF-II binding domain of the early vertebrate fugu fish and expressed it in bacteria. A 72000 Da truncated receptor containing the IGF-II binding domain was obtained...
January 30, 2018: International Journal of Biological Macromolecules
Cecilia H A Gouveia, Manuela Miranda-Rodrigues, Gisele M Martins, Bianca Neofiti-Papi
Thyroid hormone (TH) is essential for skeletal development from the late fetal life to the onset of puberty. During this large window of actions, TH has key roles in endochondral and intramembranous ossifications and in the longitudinal bone growth. There is evidence that TH acts directly in skeletal cells but also indirectly, specially via the growth hormone/insulin-like growth factor-1 axis, to control the linear skeletal growth and maturation. The presence of receptors, plasma membrane transporters, and activating and inactivating enzymes of TH in skeletal cells suggests that direct actions of TH in these cells are crucial for skeletal development, which has been confirmed by several in vitro and in vivo studies, including mouse genetic studies, and clinical studies in patients with resistance to thyroid hormone due to dominant-negative mutations in TH receptors...
2018: Vitamins and Hormones
David Aguado-Llera, Sandra Canelles, Laura M Frago, Julie A Chowen, Jesús Argente, Eduardo Arilla, Vicente Barrios
Somatostatin (SRIF), a neuropeptide highly distributed in the hippocampus and involved in learning and memory, is markedly reduced in the brain of Alzheimer's disease patients. The effects of insulin-like growth factor-I (IGF-I) against β amyloid (Aβ)-induced neuronal death and associated cognitive disorders have been extensively reported in experimental models of this disease. Here, we examined the effect of IGF-I on the hippocampal somatostatinergic system in Aβ-treated rats and the molecular mechanisms associated with changes in this peptidergic system...
February 2, 2018: Neuroscience
Yasmine Neirijnck, Pierre Calvel, Karen R Kilcoyne, Françoise Kühne, Isabelle Stévant, Richard J Griffeth, Jean-Luc Pitetti, Silvana A Andric, Meng-Chun Hu, François Pralong, Lee B Smith, Serge Nef
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, and testicular function. Notably, the IGF system has been reported to mediate the proliferation of steroidogenic cells. However, the precise role and contribution of the membrane receptors mediating those effects, namely, insulin receptor (INSR) and type-I insulin-like growth factor receptor (IGF1R), have not, to our knowledge, been investigated. We show here that specific deletion of both Insr and Igf1r in steroidogenic cells in mice leads to severe alterations of adrenocortical and testicular development...
January 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ye Yang, Wei Bao, Zhengyu Sang, Yongbing Yang, Meng Lu, Xiaowei Xi
Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways...
February 2018: Oncology Letters
Cheng Yajun, Tang Yuan, Wang Zhong, Xu Bin
The present study aimed to identify potential genes associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP) in order to improve the prediction of the prognosis of patients with PCa. The GSE25136 microarray dataset, including 39 recurrent and 40 non-recurrent PCa samples, was downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) were identified using limma packages, and the pheatmap package was used to present the DEGs screened using a hierarchical cluster analysis...
January 2018: Experimental and Therapeutic Medicine
Sreemathi Logan, Gavin A Pharaoh, M Caleb Marlin, Dustin R Masser, Satoshi Matsuzaki, Benjamin Wronowski, Alexander Yeganeh, Eileen E Parks, Pavithra Premkumar, Julie A Farley, Daniel B Owen, Kenneth M Humphries, Michael Kinter, Willard M Freeman, Luke I Szweda, Holly Van Remmen, William E Sonntag
OBJECTIVE: A decline in mitochondrial function and biogenesis as well as increased reactive oxygen species (ROS) are important determinants of aging. With advancing age, there is a concomitant reduction in circulating levels of insulin-like growth factor-1 (IGF-1) that is closely associated with neuronal aging and neurodegeneration. In this study, we investigated the effect of the decline in IGF-1 signaling with age on astrocyte mitochondrial metabolism and astrocyte function and its association with learning and memory...
February 1, 2018: Molecular Metabolism
Francesca Cirillo, Pietro Lazzeroni, Cecilia Catellani, Chiara Sartori, Sergio Amarri, Maria Elisabeth Street
MicroRNAs are involved in multiple pathophysiological networks and in the pathogenesis of a broad spectrum of human disorders, including cancer and inflammatory diseases. Impaired linear growth is encountered in children with chronic inflammatory conditions such as cystic fibrosis, inflammatory bowel diseases, juvenile idiopathic arthritis, celiac disease and in subjects born intrauterine growth restricted/small for gestational age. Children with inflammatory conditions may also be at risk of developing insulin resistance as a result of the inflammatory process and concurrent therapy...
February 2, 2018: Cytokine & Growth Factor Reviews
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