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FGF Receptor

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https://www.readbyqxmd.com/read/28101211/receptor-fgfrl1-acts-as-a-tumor-suppressor-in-nude-mice-when-overexpressed-in-hek-293-tet-on-cells
#1
Lei Zhuang, Florian Steinberg, Beat Trueb
Fibroblast growth factor receptor-like 1 (FGFRL1) is a transmembrane receptor that interacts with heparin and FGF ligands. In contrast to the classical FGF receptors, FGFR1 to FGFR4, it does not appear to affect cell growth and proliferation. In the present study, an inducible gene expression system was utilized in combination with a xenograft tumor model to investigate the effects of FGFRL1 on cell adhesion and tumor formation. It was determined that recombinant FGFRL1 promotes the adhesion of HEK 293 Tet-On(®) cells in vitro...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28095739/expression-and-localization-of-fibroblast-growth-factor-fgf-23-and-klotho-in-the-spleen-its-physiological-and-functional-implications
#2
Yuri Nakashima, Toru Mima, Mitsuru Yashiro, Tomohiro Sonou, Masaki Ohya, Asuka Masumoto, Shintaro Yamanaka, Daisuke Koreeda, Koichi Tatsuta, Yoshiyuki Hanba, Mari Moribata, Shigeo Negi, Takashi Shigematsu
The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220(+) CD21/CD35(+) CD1d(+) CD43(-) marginal zone B cells...
January 18, 2017: Growth Factors
https://www.readbyqxmd.com/read/28094278/persistent-fibroblast-growth-factor-23-signalling-in-the-parathyroid-glands-for-secondary-hyperparathyroidism-in-mice-with-chronic-kidney-disease
#3
Kazuki Kawakami, Ai Takeshita, Kenryo Furushima, Masayasu Miyajima, Ikuji Hatamura, Makoto Kuro-O, Yasuhide Furuta, Kazushige Sakaguchi
Secondary hyperparathyroidism, in which parathyroid hormone (PTH) is excessively secreted in response to factors such as hyperphosphataemia, hypocalcaemia, and low 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, is commonly observed in patients with chronic kidney disease (CKD), and is accompanied by high levels of fibroblast growth factor 23 (FGF23). However, the effect of FGF23 on the parathyroid glands (PG) remains controversial. To bind to FGF receptors, FGF23 requires αKlotho, which is highly expressed in the PG...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093295/in-silico-enhancement-of-the-stability-and-activity-of-keratinocyte-growth-factor
#4
Mansour Poorebrahim, Solmaz Sadeghi, Raziyeh Ghorbani, Matin Asghari, Mohammad Foad Abazari, Hourieh Kalhor, Hamzeh Rahimi
Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family, has been implicated in some biological processes such as cell proliferation, development and differentiation. High mitogenic activity of this protein has made it very suitable for repairing radiation-and chemotherapy-induced damages. KGF, which has been developed from human KGF, is clinically applied to reduce the incidence and duration of cancer therapeutic agents. However, the activity of KGF is limited during treatment due to its poor stability...
January 13, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#5
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
December 27, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#6
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#7
Jan Freark de Boer, Marleen Schonewille, Marije Boesjes, Henk Wolters, Vincent W Bloks, Trijnie Bos, Theo H van Dijk, Angelika Jurdzinski, Renze Boverhof, Justina C Wolters, Jan A Kuivenhoven, Jan M van Deursen, Ronald P J Oude Elferink, Antonio Moschetta, Claus Kremoser, Henkjan J Verkade, Folkert Kuipers, Albert K Groen
BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway are, however, poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28060761/identification-of-micrornas-associated-with-glioma-diagnosis-and-prognosis
#8
Xinyun Ye, Wenjin Wei, Zhengyu Zhang, Chunming He, Ruijin Yang, Jinshi Zhang, Zhiwu Wu, Qianliang Huang, Qiuhua Jiang
The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057484/type-ii-cgmp-dependent-protein-kinase-negatively-regulates-fibroblast-growth-factor-signaling-by-phosphorylating-raf-1-at-serine-43-in-rat-chondrosarcoma-cells
#9
Norio Kamemura, Sara Murakami, Hiroaki Komatsu, Masahiro Sawanoi, Kenji Miyamoto, Kazumi Ishidoh, Koji Kishimoto, Akihiko Tsuji, Keizo Yuasa
Although type II cGMP-dependent protein kinase (PKGII) is a major downstream effector of cGMP in chondrocytes and attenuates the FGF receptor 3/ERK signaling pathway, its direct target proteins have not been fully explored. In the present study, we attempted to identify PKGII-targeted proteins, which are associated with the inhibition of FGF-induced MAPK activation. Although FGF2 stimulation induced the phosphorylation of ERK1/2, MEK1/2, and Raf-1 at Ser-338 in rat chondrosarcoma cells, pretreatment with a cell-permeable cGMP analog strongly inhibited their phosphorylation...
January 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#10
Jun Zhang, Jamila Gupte, Yan Gong, Jennifer Weiszmann, Yuan Zhang, Ki Jeong Lee, William G Richards, Yang Li
Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28041631/targeting-fibroblast-growth-factor-pathways-in-endometrial-cancer
#11
Boris Winterhoff, Gottfried E Konecny
Novel treatments that improve outcomes for patients with recurrent or metastatic endometrial cancer (EC) remain an unmet need. Aberrant signaling by fibroblast growth factors (FGFs) and FGF receptors (FGFRs) has been implicated in several human cancers. Activating mutations in FGFR2 have been found in up to 16% of ECs, suggesting an opportunity for targeted therapy. This review summarizes the role of the FGF pathway in angiogenesis and EC, and provides an overview of FGFR-targeted therapies under clinical development for the treatment of EC...
November 11, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28031461/heparan-sulfate-domains-required-for-fibroblast-growth-factor-1-and-2-signaling-through-fibroblast-growth-factor-receptor-1c
#12
Victor Schultz, Mathew Suflita, Xinyue Liu, Xing Zhang, Yanlei Yu, Lingyun Li, Dixy E Green, Yongmei Xu, Fuming Zhang, Paul L DeAngelis, Jian Liu, Robert J Linhardt
A small library, of well-defined heparan sulfate (HS) polysaccharides, was chemoenzymatically synthesized and used for a detailed structure-activity study of fibroblast growth factor (FGF)1 and FGF2 signaling through FGF receptor (FGFR)1c. The HS polysaccharide tested contained both undersulfated (NA) domains and highly sulfated (NS) domains as well as very well defined non-reducing termini. This study examines differences in the HS selectivity of the positive canyons of the FGF12-FGFR1c2 and FGF22-FGFR1c2 HS-binding sites of the symmetric FGF2-FGFR2HS2 signal transduction complex...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28030802/inhibition-of-the-fibroblast-growth-factor-receptor-fgfr-pathway-the-current-landscape-and-barriers-to-clinical-application
#13
REVIEW
Young Kwang Chae, Keerthi Ranganath, Peter S Hammerman, Christos Vaklavas, Nisha Mohindra, Aparna Kalyan, Maria Matsangou, Ricardo Costa, Benedito Carneiro, Victoria M Villaflor, Massimo Cristofanilli, Francis J Giles
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) is a tyrosine kinase signaling pathway that has a fundamental role in many biologic processes including embryonic development, tissue regeneration, and angiogenesis. Increasing evidence indicates that this pathway plays a critical role in oncogenesis via gene amplification, activating mutations, or translocation in tumors of various histologies. With multiplex sequencing technology, the detection of FGFR aberrations has become more common and is tied to cancer cell proliferation, resistance to anticancer therapies, and neoangiogenesis...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28026804/-role-of-fibroblast-growth-factors-in-pancreatic-cancer
#14
REVIEW
D A Gnatenko, E P Kopantsev, E D Sverdlov
Fibroblast growth factors belong to a family of growth factors that are involved in various processes in organism and have a wide range of biological functions. Specifically for pancreas, FGFs are important during both organogenesis and carcinogenesis. One of the main characteristic of pancreatic cancer, is it close interaction between cancer and stromal cells via different factors, including FGF. Pathological changes in FGF/FGFR signaling pathway is a complex process. The remodeling effects and stimulation of tumor growth are mostly depend not only on types of receptors, but also from their isoforms...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28011645/in-vitro-and-in-vivo-analyses-reveal-profound-effects-of-fibroblast-growth-factor-16-as-a-metabolic-regulator
#15
Ingrid C Rulifson, Patrick Collins, Li Miao, Dana Nojima, Ki Jeong Lee, Miki Hardy, Jamila Gupte, Kelly Hensley, Kim Samayoa, Cynthia Cam, James B Rottman, Mike Ollmann, William G Richards, Yang Li
The discovery of brown adipose tissue (BAT) as a key regulator of energy expenditure has sparked interest in identifying novel soluble factors capable of activating inducible BAT (iBAT) to combat obesity. Using a high content cell-based screen, we identified Fibroblast Growth Factor (FGF) 16 as a potent inducer of several physical and transcriptional characteristics analogous to those of both classical BAT and iBAT. Over-expression of Fgf16 in vivo recapitulated several of our in vitro findings, specifically significant induction of Ucp1 gene and UCP1 protein expression in inguinal white adipose tissue (iWAT), a common site for emergent active iBAT...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28008155/combination-treatment-of-prostate-cancer-with-fgf-receptor-and-akt-kinase-inhibitors
#16
Shu Feng, Longjiang Shao, Patricia Castro, Ilsa Coleman, Peter S Nelson, Paul D Smith, Barry R Davies, Michael Ittmann
Activation of the PI3K/AKT pathway occurs in the vast majority of advanced prostate cancers (PCas). Activation of fibroblast growth factor receptor (FGFR) signaling occurs in a wide variety of malignancies, including PCa. RNA-Seq of castration resistant PCa revealed expression of multiple FGFR signaling components compatible with FGFR signaling in all cases, with multiple FGF ligands expressed in 90% of cases. Immunohistochemistry confirmed FGFR signaling in the majority of xenografts and advanced PCas. AZD5363, an AKT kinase inhibitor and AZD4547, a FGFR kinase inhibitor are under active clinical development...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28002451/investigating-the-potential-signaling-pathways-that-regulate-activation-of-the-novel-pkc-downstream-of-serotonin-in-aplysia
#17
Carole A Farah, Bryan Rourke, Unkyung Shin, Larissa Ferguson, María José Luna, Wayne S Sossin
Activation of the novel PKC Apl II in sensory neurons by serotonin (5HT) underlies the ability of 5HT to reverse synaptic depression, but the pathway from 5HT to PKC Apl II activation remains unclear. Here we find no evidence for the Aplysia-specific B receptors, or for adenylate cyclase activation, to translocate fluorescently-tagged PKC Apl II. Using an anti-PKC Apl II antibody, we monitor translocation of endogenous PKC Apl II and determine the dose response for PKC Apl II translocation, both in isolated sensory neurons and sensory neurons coupled with motor neurons...
2016: PloS One
https://www.readbyqxmd.com/read/27992319/therapeutics-targeting-fgf-signaling-network-in-human-diseases
#18
REVIEW
Masaru Katoh
Fibroblast growth factor (FGF) signaling through its receptors, FGFR1, FGFR2, FGFR3, or FGFR4, regulates cell fate, angiogenesis, immunity, and metabolism. Dysregulated FGF signaling causes human diseases, such as breast cancer, chondrodysplasia, gastric cancer, lung cancer, and X-linked hypophosphatemic rickets. Recombinant FGFs are pro-FGF signaling therapeutics for tissue and/or wound repair, whereas FGF analogs and gene therapy are under development for the treatment of cardiovascular disease, diabetes, and osteoarthritis...
December 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27988457/in-vitro-and-in-vivo-activity-of-lucitanib-in-fgfr1-2-amplified-or-mutated-cancer-models
#19
Federica Guffanti, Rosaria Chilà, Ezia Bello, Massimo Zucchetti, Monique Zangarini, Laura Ceriani, Mariella Ferrari, Monica Lupi, Anne Jacquet-Bescond, Mike F Burbridge, Marie-Jeanne Pierrat, Giovanna Damia
The fibroblast growth factor receptor (FGFR) pathway has been implicated both as an escape mechanism from anti-angiogenic therapy and as a driver oncogene in different tumor types. Lucitanib is a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors 1 to 3 (VEGFR1 to 3), platelet derived growth factor α/β (PDGFRα/β) and FGFR1-3 tyrosine kinases and has demonstrated activity in a phase I/II clinical study, with objective RECIST responses in breast cancer patients with FGFR1 or FGF3/4/19 gene amplification, as well as in patients anticipated to benefit from anti-angiogenic agents...
December 15, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27978814/switchfinder-a-novel-method-and-query-facility-for-discovering-dynamic-gene-expression-patterns
#20
Svetlana Bulashevska, Colin Priest, Daniel Speicher, Jörg Zimmermann, Frank Westermann, Armin B Cremers
BACKGROUND: Biological systems and processes are highly dynamic. To gain insights into their functioning time-resolved measurements are necessary. Time-resolved gene expression data captures temporal behaviour of the genes genome-wide under various biological conditions: in response to stimuli, during cell cycle, differentiation or developmental programs. Dissecting dynamic gene expression patterns from this data may shed light on the functioning of the gene regulatory system. The present approach facilitates this discovery...
December 15, 2016: BMC Bioinformatics
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