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FGF Receptor

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https://www.readbyqxmd.com/read/28433771/a-versatile-tumor-gene-deletion-system-reveals-a-crucial-role-for-fgfr1-in-breast-cancer-metastasis
#1
Wei Wang, Yanling Meng, Bingning Dong, Jie Dong, Michael M Ittmann, Chad J Creighton, Lu Yang, Hong Zhang, Tao Shen, Jianghua Wang, David R Rowley, Yi Li, Fengju Chen, David D Moore, Feng Yang
RCAS avian viruses have been used to deliver oncogene expression and induce tumors in transgenic mice expressing the virus receptor TVA. Here we report the generation and characterization of a novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus designed to specifically knockout genes of interest in tumors generated in appropriate mutant mouse hosts. FGF receptor 1 (FGFR1) is a gene that is amplified in human breast cancer, but there have been no definitive studies on its function in mammary tumorigenesis, progression, and metastasis in vivo in spontaneous tumors in mice...
April 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28427515/fgfr-a-promising-druggable-target-in-cancer-molecular-biology-and-new-drugs
#2
REVIEW
Rut Porta, Roberto Borea, Andreia Coelho, Shahanavaj Khan, António Araújo, Pablo Reclusa, Tindara Franchina, Nele Van Der Steen, Peter Van Dam, Jose Ferri, Rafael Sirera, Aung Naing, David Hong, Christian Rolfo
INTRODUCTION: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. AREAS COVERED: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28417659/effects-of-nphe-1-arg-14-lys-15-n-ofq-nh2-ufp-101-a-potent-nop-receptor-antagonist-on-molecular-cellular-and-behavioural-alterations-associated-with-chronic-mild-stress
#3
Giovanni Vitale, Monica Filaferro, Maria Vittoria Micioni Di Bonaventura, Valentina Ruggieri, Carlo Cifani, Remo Guerrini, Michele Simonato, Silvia Zucchini
The present study investigated the effect of [Nphe(1)] Arg(14), Lys(15)-N/OFQ-NH2 (UFP-101), a selective NOP receptor antagonist, in chronic mild stress (CMS) in male Wistar rats. NOP receptor antagonists were reported to elicit antidepressant-like effects in rodents. Our aim was to investigate UFP-101 effects on CMS-induced anhedonia and impairment of hippocampal neurogenesis. UFP-101 (10 nmol/rat intracerebroventricularly) did not influence sucrose intake in non-stressed animals, but reinstated basal sucrose consumption in stressed animals from the second week of treatment...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28406928/fibroblast-growth-factor-23-promotes-terminal-differentiation-of-atdc5-cells
#4
Mathilde Guibert, Adeline Gasser, Hervé Kempf, Arnaud Bianchi
OBJECTIVES: Fibroblast Growth Factor 23 (FGF23) is well documented as a crucial player in the systemic regulation of phosphate homeostasis. Moreover, loss-of-function experiments have revealed that FGF23 also has a phosphate-independent and local impact on skeletogenesis. Here, we used ATDC5 cell line to investigate the expression of FGF23 and the role it may play locally during the differentiation of these cells. METHODS: ATDC5 cells were differentiated in the presence of insulin, and treated with recombinant FGF23 (rFGF23), inorganic phosphate (Pi) and/or PD173074, an inhibitor of FGF receptors (FGFRs)...
2017: PloS One
https://www.readbyqxmd.com/read/28395533/the-influence-of-occupational-chronic-lead-exposure-on-the-levels-of-selected-pro-inflammatory-cytokines-and-angiogenic-factors
#5
A Machoń-Grecka, M Dobrakowski, M Boroń, G Lisowska, A Kasperczyk, S Kasperczyk
The aim of the study was to determine the effect of occupational exposure to lead on the blood levels of pro-inflammatory cytokines and selected factors that influence angiogenesis. The study population was divided into two groups. The first group consisted of 56 male workers chronically exposed to lead. The second group (control) was comprised of 24 male administrative workers. The serum levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were significantly higher in the group of workers chronically exposed to lead compared to control values by 38%, 68%, and 57%, respectively...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28388262/investigational-drugs-targeting-fibroblast-growth-factor-receptor-in-the-treatment-of-non-small-cell-lung-cancer
#6
Erika Rijavec, Carlo Genova, Giulia Barletta, Federica Biello, Giovanni Rossi, Marco Tagliamento, Maria Giovanna Dal Bello, Simona Coco, Irene Vanni, Simona Boccardo, Angela Alama, Francesco Grossi
Fibroblast growth factor receptor (FGFR) due to its central role in regulating cell survival, is a promising target for cancer therapeutics. Dysregulation of the FGFR pathway has been observed in several malignancies, including non-small cell lung cancer (NSCLC) particularly in patients with squamous histology. Areas covered: The aim of this article is to review the most relevant findings of clinical trials investigating drugs targeting FGFR pathway: such as FGFR tyrosine kinase inhibitors (TKIs), FGFR monoclonal antibodies and FGF ligand traps in NSCLC patients...
April 7, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28377558/pentraxin-3-as-a-new-indicator-of-cardiovascular%C3%A2-related-death-in-patients-with-advanced-chronic-kidney-disease
#7
Marcin Krzanowski, Katarzyna Krzanowska, Mariusz Gajda, Paulina Dumnicka, Artur Dziewierz, Karolina Woziwodzka, Jan A Litwin, Władysław Sułowicz
INTRODUCTION    Pentraxin3 (PTX3) play an important role in the inflammatory response, taking part in recognizing pathogens and damaged tissues. OBJECTIVES    The aim of the study was to assess the relationship between PTX3 levels and all-cause and cardiovascular (CV) mortality in chronic kidney disease (CKD) patients during five-year observation period.  PATIENTS AND METHODS    The study comprised 78 patients (51 hemodialyzed, 27 predialysis). The examined parameters included PTX3, calcium, phosphate, iPTH, interleukin-6 (IL-6), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin, tumor necrosis factor receptor II (TNF-R II), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), stromal cell-derived factor α (SDF1α), and thrombomodulin (TM)...
February 27, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28369079/polarization-and-migration-in-the-zebrafish-posterior-lateral-line-system
#8
Hildur Knutsdottir, Cole Zmurchok, Dhananjay Bhaskar, Eirikur Palsson, Damian Dalle Nogare, Ajay B Chitnis, Leah Edelstein-Keshet
Collective cell migration plays an important role in development. Here, we study the posterior lateral line primordium (PLLP) a group of about 100 cells, destined to form sensory structures, that migrates from head to tail in the zebrafish embryo. We model mutually inhibitory FGF-Wnt signalling network in the PLLP and link tissue subdivision (Wnt receptor and FGF receptor activity domains) to receptor-ligand parameters. We then use a 3D cell-based simulation with realistic cell-cell adhesion, interaction forces, and chemotaxis...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28364143/clump-formation-in-mouse-pituitary-derived-non-endocrine-cell-line-tpit-f1-promotes-differentiation-into-growth-hormone-producing-cells
#9
Masashi Higuchi, Saishu Yoshida, Naoko Kanno, Hideo Mitsuishi, Hiroki Ueharu, Mo Chen, Naoto Nishimura, Takako Kato, Yukio Kato
The adenohypophysis comprises six types of endocrine cells, including PIT1-lineage cells such as growth hormone (GH)-producing cells and heterogeneous non-endocrine cells, such as pituitary stem/progenitor cells as a source of endocrine cells. We determine the expression of characteristic stem cell marker genes, including sex-determining region Y-box 2 (Sox2), in mouse pituitary-derived non-endocrine cell lines Tpit/E, Tpit/F1 and TtT/GF. We observed high expression of fibroblast growth factor (FGF) receptors in Tpit/F1 cells, which we characterised by cultivation in medium containing a basic FGF and B27 supplement as used for neural stem-cell differentiation...
March 31, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28359915/sp3-controls-fibroblast-growth-factor-receptor-4-gene-activity-during-myogenic-differentiation
#10
Eric Cavanaugh, Joseph X DiMario
Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling is a critical component in the regulation of myoblast proliferation and differentiation. The transient FGFR4 gene expression during the transition from proliferating myoblasts to differentiated myotubes indicates that FGFR4 regulates this critical phase of myogenesis. The Specificity Protein (SP) family of transcription factors controls FGFR family member gene activity. We sought to determine if members of the Sp family regulate mouse FGFR4 gene activity during myogenic differentiation...
March 27, 2017: Gene
https://www.readbyqxmd.com/read/28350116/selective-fgfr-inhibitor-bgj398-inhibits-phosphorylation-of-akt-and-stat3-and-induces-cytotoxicity-in-sphere-cultured-ovarian-cancer-cells
#11
Hwa Jun Cha, Jung Hye Choi, In Chul Park, Chun Ho Kim, Sung Kwan An, Tae Jin Kim, Jae Ho Lee
Epithelial ovarian cancer is the most aggressive and lethal among the gynecological malignancies, which is often found disseminated to peritoneal cavity at the time of diagnosis. There is accumulating evidence on the existence of genetic alteration and amplification of fibroblast growth factor receptor (FGFR) in various cancers. Also the aberrated FGFR/FGF signaling has been implicated in cancer development and tumor microenvironment. However, the antitumor activity of BGJ398, a selective inhibitor of FGFR 1/2/3 against ovarian cancer still remains unknown...
March 15, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28348168/fgfr2-is-required-for-airway-basal-cell-self-renewal-and-terminal-differentiation
#12
Gayan Balasooriya, Maja Goschorska, Eugenia Piddini, Emma L Rawlins
Airway stem cells slowly self-renew and produce differentiated progeny to maintain homeostasis throughout the life-span of an individual. Mutations in the molecular regulators of these processes may drive cancer or degenerative disease, but are also potential therapeutic targets. Conditionally deleting one copy of FGF Receptor 2 in adult mouse airway basal cells results in self-renewal and differentiation phenotypes. We show that FGFR2 signalling correlates with maintenance of expression of a key transcription factor for basal cell self-renewal and differentiation, SOX2...
March 27, 2017: Development
https://www.readbyqxmd.com/read/28346348/vitamin-d-in-chronic-kidney-disease-and-dialysis-patients
#13
REVIEW
Guillaume Jean, Jean Claude Souberbielle, Charles Chazot
Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue...
March 25, 2017: Nutrients
https://www.readbyqxmd.com/read/28341788/discovery-and-pharmacological-characterization-of-jnj-42756493-erdafitinib-a-functionally-selective-small-molecule-fgfr-family-inhibitor
#14
Timothy P S Perera, Eleonora Jovcheva, Laurence Mevellec, Jorge Vialard, Desiree De Lange, Tinne Verhulst, Caroline Paulussen, Kelly Van De Ven, Peter King, Eddy Freyne, David C Rees, Matthew Squires, Gordon Saxty, Martin Page, Ron Gilissen, Christopher W Murray, George Ward, Neil T Thompson, David R Newell, Na Cheng, Liang Xie, Jennifer Yang, Suso J Platero, Jayaprakash D Karkera, Christopher Moy, Patrick Angibaud, Sylvie Laquerre, Matthew V Lorenzi
Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases...
March 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28341272/kidney-fibroblast-growth-factor-23-does-not-contribute-to-elevation-of-its-circulating-levels-in-uremia
#15
Maria L Mace, Eva Gravesen, Anders Nordholm, Jacob Hofman-Bang, Thomas Secher, Klaus Olgaard, Ewa Lewin
Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia...
March 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28339837/vitamin-d-treatment-attenuates-cardiac-fgf23-fgfr4-signaling-and-hypertrophy-in-uremic-rats
#16
Maren Leifheit-Nestler, Alexander Grabner, Laura Hermann, Beatrice Richter, Karin Schmitz, Dagmar-Christiane Fischer, Christopher Yanucil, Christian Faul, Dieter Haffner
Background.: Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. Methods...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339036/fgf7-fgfr2-signal-promotes-invasion-and-migration-in-human-gastric-cancer-through-upregulation-of-thrombospondin-1
#17
Tingting Huang, Lei Wang, Dian Liu, Piao Li, Huihua Xiong, Liang Zhuang, Li Sun, Xianglin Yuan, Hong Qiu
Fibroblast growth factor 7 (FGF7) is a mesenchyme-specific heparin-binding growth factor that binds FGF receptor 2 (FGFR2) to regulate numerous cellular and physiological processes. FGF7/FGFR2 signal is associated with gastric cancer progression. In the present study, we investigated the molecular mechanism by which FGF7/FGFR2 promotes invasion and migration in human gastric cancer. We first demonstrated that increased FGFR2 expression in human gastric cancer tissues was significantly associated with tumor depth and clinical stage in human gastric cancer tissues...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#18
REVIEW
Zhe Huang, Aimin Xu, Bernard M Y Cheung
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28327938/targeting-the-fibroblast-growth-factor-receptor-2-in-gastric-cancer-promise-or-pitfall
#19
C Hierro, M Alsina, M Sánchez, V Serra, J Rodon, J Tabernero
Gastric cancer is the third leading cause of death from cancer worldwide. Systemic chemotherapy remains the mainstay therapeutic option for this poor prognosis cancer. Trastuzumab, the epidermal growth factor receptor 2 (ERBB2 or HER2)-antibody, is the only biological agent approved for the molecularly-selected population of HER2-positive gastric cancer patients. Over the last decade, several groups have been working for deepening into the molecular characterization of gastric cancer, shedding some light into the heterogeneity of this tumour...
March 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28324011/a-novel-fc-fgf21-with-improved-resistance-to-proteolysis-increased-affinity-towards-%C3%AE-klotho-and-enhanced-efficacy-in-mice-and-cynomolgus-monkeys
#20
Shanaka Stanislaus, Randy Hecht, Junming Yie, Todd Hager, Michael Hall, Chris Spahr, Wei Wang, Jennifer Weiszmann, Yang Li, Liying Deng, Dwight Winters, Stephen Smith, Lei Zhou, Yuesheng Li, Murielle M Véniant, Jing Xu
FGF21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We demonstrate, by introducing one additional mutation located at the C-terminus of FGF21 (A180E) that the new molecule, Fc-FGF21(RGE), has gained many improved attributes...
January 26, 2017: Endocrinology
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