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FGF Receptor

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https://www.readbyqxmd.com/read/27895121/neuronal-mtorc1-is-required-for-maintaining-the-nonreactive-state-of-astrocytes
#1
Yue Zhang, Song Xu, Kang-Yan Liang, Kai Li, Zhi-Peng Zou, Cui-Lan Yang, Kang Tan, Xiong Cao, Yu Jiang, Tian-Ming Gao, Xiao-Chun Bai
Astrocytes respond to central nervous system (CNS) insults through reactive astrogliosis, but the underlying mechanisms are unclear. In this study, we show that inactivation of mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller soma and fewer dendrites, resulting in microcephaly and aberrant behavior in adult mice...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27893433/regulation-of-brachyury-by-fibroblast-growth-factor-receptor-1-in-lung-cancer
#2
Yunping Hu, Xin Feng, Akiva Mintz, W Jeffrey Petty, Wesley Hsu
Recent evidence suggests that T-box transcription factor brachyury plays an important role in lung cancer development and progression. However, the mechanisms underlying brachyury-driven cellular processes remain unclear. Here we found that fibroblast growth factor receptor 1/mitogen-activated protein kinase (FGFR1/MAPK) signaling regulated brachyury in lung cancer. Analysis of FGFR1-4 and brachyury expression in human lung tumor tissue and cell lines found that only expression of FGFR1 was positively correlated with brachyury expression...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879395/a-computationally-identified-compound-antagonizes-excess-fgf-23-signaling-in-renal-tubules-and-a-mouse-model-of-hypophosphatemia
#3
Zhousheng Xiao, Demian Riccardi, Hector A Velazquez, Ai L Chin, Charles R Yates, Jesse D Carrick, Jeremy C Smith, Jerome Baudry, L Darryl Quarles
Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex...
November 22, 2016: Science Signaling
https://www.readbyqxmd.com/read/27878865/fibroblast-growth-factor-21-night-watch-advances-and-uncertainties-in-the-field
#4
REVIEW
A Kharitonenkov, R DiMarchi
Fibroblast growth factor (FGF) 21 belongs to a hormone-like subgroup within the FGF superfamily. The members of this subfamily, FGF19, FGF21 and FGF23, are characterized by their reduced binding affinity for heparin that enables them to be transported in the circulation and function in an endocrine manner. It is likely that FGF21 also acts in an autocrine and paracrine fashion, as multiple organs can produce this protein and its plasma concentration seems to be below the level necessary to induce a pharmacological effect...
November 22, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27872325/the-molecular-circuit-regulating-tooth-development-in-crocodilians
#5
S Tsai, A Abdelhamid, M K Khan, A Elkarargy, R B Widelitz, C M Chuong, P Wu
Alligators have robust regenerative potential for tooth renewal. In contrast, extant mammals can either renew their teeth once (diphyodont dentition, as found in humans) or not at all (monophyodont dentition, present in mice). Previously, the authors used multiple mitotic labeling to map putative stem cells in alligator dental laminae, which contain quiescent odontogenic progenitors. The authors demonstrated that alligator tooth cycle initiation is related to β-catenin/Wnt pathway activity in the dental lamina bulge...
December 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27858202/computational-drill-down-on-fgf1-heparin-interactions-through-methodological-evaluation
#6
Sándor Babik, Sergey A Samsonov, M Teresa Pisabarro
Glycosaminoglycans (GAGs) exhibit a key role in cellular communication processes through interactions with target proteins of the extracellular matrix (ECM). The sandwich-like interaction established between Fibroblast growth factor (FGF) and heparin (HE) represents quite a peculiar protein-GAG-protein system, which has been both structurally and functionally intensively studied. The molecular recognition characteristics of this system have been exploited in various computational studies in order to deepen understanding of GAG-protein interactions...
November 17, 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27849387/serum-levels-of-f%C3%A4-broblast-growth-factor-23-osteoproteger%C3%A4-n-and-receptor-act%C3%A4-vator-of-nuclear-factor-kappa-b-l%C3%A4-gand-rankl-%C3%A4-n-pat%C3%A4-ents-w%C3%A4-h-prolact%C3%A4-noma
#7
Muyesser Sayki Arslan, Mustafa Sahin, Melia Karakose, Esra Tutal, Oya Topaloglu, Bekir Ucan, Taner Demirci, Mustafa Caliskan, Seyda Sahingol, Mustafa Ozbek, Erman Cakal
PURPOSE: The aim of this study to was to evaluate the effect of fibroblast growth factor-23 (FGF-23), osteoprotegerin (OPG), receptor activator nuclear kB ligand (RANKL), and vitamin D hormones on bone loss in patients with hyperprolactinemia due to the pituitary prolactinoma. METHODS: 46 premenopausal female patients with prolactinoma and age and sex matched healthy controls (Group 3, n=20) were recruited to this cross sectional study. Prolactinoma patients were divided into two groups as patients newly diagnosed (Group 1, n=26), and under cabergoline treatment (Group 2, n=20)...
November 16, 2016: Endocrine Practice
https://www.readbyqxmd.com/read/27825137/fgfr-signaling-maintains-a-drug-persistent-cell-population-following-epithelial-mesenchymal-transition
#8
Wells S Brown, Saeed Salehin Akhand, Michael K Wendt
An emerging characteristic of drug resistance in cancer is the induction of epithelial-mesenchymal transition (EMT). However, the mechanisms of EMT-mediated drug resistance remain poorly defined. Therefore, we conducted long-term treatments of human epidermal growth factor receptor-2 (Her2)-transformed breast cancer cells with either the EGFR/Her2 kinase inhibitor, Lapatinib or TGF-β, a known physiological inducer of EMT. Both of these treatment regimes resulted in robust EMT phenotypes, but upon withdrawal a subpopulation of TGF-β induced cells readily underwent mesenchymal-epithelial transition, where as Lapatinib-induced cells failed to reestablish an epithelial population...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27816457/inhibition-of-fgf-signaling-accelerates-neural-crest-cell-differentiation-of-human-pluripotent-stem-cells
#9
Thiranut Jaroonwitchawan, Pattamon Muangchan, Parinya Noisa
Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27815219/existence-of-muscarinic-acetylcholine-receptor-machr-and-fibroblast-growth-factor-receptor-fgfr-heteroreceptor-complexes-and-their-enhancement-of-neurite-outgrowth-in-neural-hippocampal-cultures
#10
V Di Liberto, D O Borroto-Escuela, M Frinchi, V Verdi, K Fuxe, N Belluardo, G Mudò
BACKGROUND: Recently, it was demonstrated that G-protein-coupled receptors (GPCRs) can transactivate tyrosine kinase receptors in absence of their ligands. In this work, driven by the observation that mAChRs and fibroblast growth factor receptors (FGFRs) share signalling pathways and regulation of brain functions, it was decided to explore whether mAChRs activation may transactivate FGFRs and, if so, to characterize the related trophic effects in cultured hippocampal neurons. METHODS: Oxotremorine-M transactivation of FGFRs and related trophic effects were tested in primary hippocampal neurons...
November 1, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27815159/expression-and-functional-role-of-bone-morphogenetic-proteins-bmps-in-cyclical-corpus-luteum-in-buffalo-bubalus-bubalis
#11
G Rajesh, Avishek Paul, S R Mishra, Jaya Bharati, Nipuna Thakur, Tanmay Mondal, Sanjhali Soren, S Harikumar, K Narayanan, V S Chouhan, Sadhan Bag, B C Das, G Singh, V P Maurya, G Taru Sharma, Mihir Sarkar
The role of growth factors in the modulation of ovarian function is an interesting area of research in reproductive biology. Recently, we have shown the expression and role of IGF, EGF, VEGF and FGF in the follicle and CL. Here, we report the presence of Bone Morphogenetic Proteins (BMPs) and their functional receptors in the corpus luteum (CL) of buffalo. The bubaline CL was classified into four stages according to the morphology and progesterone (P4) concentration. The qPCR, immunoblot and immunohistochemistry studies revealed that BMP2 and BMP Receptors (BMPR1A, BMPR1B and BMPR2) were significantly upregulated during the mid stage whereas BMP4 and BMP7 were upregulated during the early stage of CL (P<0...
January 1, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27800477/growth-factor-content-in-human-sera-affects-the-isolation-of-mesangiogenic-progenitor-cells-mpcs-from-human-bone-marrow
#12
Marina Montali, Serena Barachini, Francesca M Panvini, Vittoria Carnicelli, Franca Fulceri, Iacopo Petrini, Simone Pacini
Mesangiogenic Progenitor Cells (MPCs) are human bone marrow-derived multipotent cells, isolated in vitro under selective culture conditions and shown to retain both mesengenic and angiogenic potential. MPCs also co-isolated with multipotent stromal cells (MSCs) when bone marrow primary cultures were set up for clinical applications, using human serum (HS) in place of fetal bovine serum (FBS). MPC culture purity (over 95%) is strictly dependent on HS supplementation with significant batch-to-batch variability...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27799550/targeting-of-ras-mediated-fgf-signaling-suppresses-pten-deficient-skin-tumor
#13
Grinu Mathew, Abdul Hannan, Kristina Hertzler-Schaefer, Fen Wang, Gen-Sheng Feng, Jian Zhong, Jean J Zhao, Julian Downward, Xin Zhang
Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified an autocrine FGF signaling induced by loss of Pten in keratinocytes. In this study, we demonstrate that skin hyperplasia requires FGF receptor adaptor protein Frs2α and tyrosine phosphatase Shp2, two upstream regulators of Ras signaling. Although the PI3-kinase regulatory subunits p85α and p85β are dispensable, the PI3-kinase catalytic subunit p110α requires interaction with Ras to promote hyperplasia in Pten-deficient skin, thus demonstrating an important cross-talk between Ras and PI3K pathways...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27795708/broad-spectrum-anticancer-activity-of-myo-inositol-and-inositol-hexakisphosphate
#14
REVIEW
Mariano Bizzarri, Simona Dinicola, Arturo Bevilacqua, Alessandra Cucina
Inositols (myo-inositol and inositol hexakisphosphate) exert a wide range of critical activities in both physiological and pathological settings. Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways. Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle. Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27787957/epiprofin-regulates-enamel-formation-and-tooth-morphogenesis-by-controlling-epithelial-mesenchymal-interactions-during-tooth-development
#15
Takashi Nakamura, Lucia Jimenez-Rojo, Eiki Koyama, Maurizio Pacifici, Susana de Vega, Masahiro Iwamoto, Satoshi Fukumoto, Fernando Unda, Yoshihiko Yamada
The synchronization of cell proliferation and cytodifferentiation between dental epithelial and mesenchymal cells is required for the morphogenesis of teeth with the correct functional shapes and optimum sizes. Epiprofin (Epfn), a transcription factor belonging to the Sp family, regulates dental epithelial cell proliferation and is essential for ameloblast and odontoblast differentiation. Epfn deficiency results in the lack of enamel and ironically the formation of extra teeth. We investigated the mechanism underlying the functions of Epfn in tooth development through the creation of transgenic mice expressing Epfn under the control of an epithelial cell-specific K5 promoter, (K5-Epfn)...
October 27, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27773526/an-s116r-phosphorylation-site-mutation-in-human-fibroblast-growth-factor-1-differentially-affects-mitogenic-and-glucose-lowering-activities
#16
Xue Xia, Ozan S Kumru, Sachiko I Blaber, C Russell Middaugh, Ling Li, David M Ornitz, Jae Myoung Suh, Annette R Atkins, Michael Downes, Ronald M Evans, Connie A Tenorio, Ewa Bienkiewicz, Michael Blaber
Fibroblast growth factor-1 (FGF-1), a potent human mitogen and insulin sensitizer, signals through both tyrosine kinase receptor-mediated autocrine/paracrine pathways as well as a nuclear intracrine pathway. Phosphorylation of FGF-1 at serine 116 (S116) has been proposed to regulate intracrine signaling. Position S116 is located within a ∼17 amino acid C-terminal loop that contains a rich set of functional determinants including heparin∖heparan sulfate affinity, thiol reactivity, nuclear localization, pharmacokinetics, functional half-life, nuclear ligand affinity, stability, and structural dynamics...
December 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27771610/a-phase-ii-study-of-tivozanib-in-patients-with-metastatic-and-nonresectable-soft-tissue-sarcomas
#17
M Agulnik, R L B Costa, M Milhem, A W Rademaker, B C Prunder, D Daniels, B T Rhodes, C Humphreys, S Abbinanti, L Nye, R Cehic, A Polish, C Vintilescu, T McFarland, K Skubitz, S Robinson, S Okuno, B A Van Tine
BACKGROUND: Soft tissue sarcomas (STSs) overexpress vascular endothelial growth factors (VEGF) and VEGF-receptors (VEGFR) activation have been associated with tumor aggressiveness. Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGFR1-3, with activity against PDGFRα/β and cKIT. The primary endpoint of this study was progression free survival (PFS) rate at 16 weeks. Secondary end points were overall survival (OS), response rate, safety and correlative studies...
October 22, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27757968/fibroblast-growth-factors-and-pulmonary-fibrosis-it-s-more-complex-than-it-sounds
#18
Kevin K Kim, Thomas H Sisson, Jeffrey C Horowitz
Lung fibrosis results from the cumulative effect of dysfunctional wound repair involving multiple cell types, including fibroblasts, epithelial cells and macrophages responding to an array of soluble and matrix mediated stimuli. Recent studies have shown that a tyrosine kinase inhibitor that targets FGF, VEGF and PDGF receptors can slow the rate of decline in pulmonary function in patients with idiopathic pulmonary fibrosis. However, each of these growth factor families is comprised of multiple ligands and receptors with pleiotropic activities on different cell types such that their broad inhibition might have both pro-fibrotic and anti-fibrotic effects, limiting the potential therapeutic efficacy...
October 19, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27755557/an-abbreviated-protocol-for-in-vitro-generation-of-functional-human-embryonic-stem-cell-derived-beta-like-cells
#19
Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
https://www.readbyqxmd.com/read/27753862/br-02-2-hypertension-management-in-cancer-patients-undergoing-chemotherapy
#20
Naftali Stern
As both the rate of hypertension and cancer rise with age, concomitant hypertension in patients receiving treatment for cancer is very common. Increase in blood pressure during cancer treatment requires careful clinical assessment. Distinction between discontinuation or malabsorption of antihypertensive treatment due to factors such as nausea/vomiting/diarrhea and anti-cancer drug specific effects must be first made. De-novo hypertension during cancer treatment is likely related to anticancer drugs per se. Classical chemotherapeutic agents such as cyclophosphamide, cisplatin and busulfan have been previously linked to rising blood pressure...
September 2016: Journal of Hypertension
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