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FGF Receptor

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https://www.readbyqxmd.com/read/28640125/targeted-sequencing-in-fgf-fgfr-genes-and-association-analysis-of-variants-for-mandibular-prognathism
#1
Xueyan Xiong, Shuyuan Li, Ying Cai, Fengshan Chen
To identify variants of the genes in fibroblast growth factors/fibroblast growth factor receptors (FGF/FGFR) signal pathway that predispose to mandibular prognathism (MP) in the general Chinese population systematically.Targeted sequencing of the FGF/FGFR genes was conducted in 176 MP individuals and 155 class I malocclusion controls. The associations of common and rare variants with MP as a categorical phenotype and also continuous malocclusion phenotypes generated by principal component (PC) analysis were analyzed...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#2
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631381/tec-controls-pluripotency-and-early-cell-fate-decisions-of-human-pluripotent-stem-cells-via-regulation-of-fgf2-secretion
#3
Tereza Vanova, Zaneta Konecna, Zuzana Zbonakova, Giuseppe La Venuta, Karolina Zoufalova, Sarka Jelinkova, Miroslav Varecha, Vladimir Rotrekl, Pavel Krejci, Walter Nickel, Petr Dvorak, Michaela Kunova Bosakova
Human pluripotent stem cells (hPSC) require signaling provided by fibroblast growth factor (FGF) receptors. This can be initiated by the recombinant FGF2 ligand supplied exogenously, but hPSC further support their niche by secretion of endogenous FGF2. In this study, we describe a role of TEC kinase (tyrosine kinase expressed in hepatocellular carcinoma) in this process. We show that TEC-mediated FGF2 secretion is essential for hPSC self-renewal, and its lack mediates specific differentiation. Following both shRNA- and siRNA-mediated TEC knock-down, hPSC secrete less FGF2...
June 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28629128/interactions-between-a-heparin-trisaccharide-library-and-fgf-1-analyzed-by-nmr-methods
#4
María José García-Jiménez, Sergio Gil-Caballero, Ángeles Canales, Jesús Jiménez-Barbero, José L de Paz, Pedro M Nieto
FGF-1 is a potent mitogen that, by interacting simultaneously with Heparan Sulfate Glycosaminoglycan HSGAG and the extracellular domains of its membrane receptor (FGFR), generates an intracellular signal that finally leads to cell division. The overall structure of the ternary complex Heparin:FGF-1:FGFR has been finally elucidated after some controversy and the interactions within the ternary complex have been deeply described. However, since the structure of the ternary complex was described, not much attention has been given to the molecular basis of the interaction between FGF-1 and the HSGAG...
June 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28616218/soluble-klotho-may-be-a-marker-of-phosphate-reabsorption
#5
Sven-Jean Tan, Edward R Smith, Stephen G Holt, Tim D Hewitson, Nigel D Toussaint
Background: Membrane-bound α-klotho functions as a co-receptor with fibroblast growth factor receptor at the renal tubule conferring specificity to fibroblast growth factor-23 (FGF-23), allowing it to inhibit tubular phosphate reabsorption at physiological concentrations. α-klotho also exists as a soluble protein. However, the complex interrelationships between soluble α-klotho (sKl), FGF-23 and phosphate reabsorption are poorly understood, with little known about the links between sKl, FGF-23 and phosphate reabsorption in chronic kidney disease (CKD)...
June 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28615947/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-etelcalcetide
#6
REVIEW
Mario Cozzolino, Andrea Galassi, Ferruccio Conte, Michela Mangano, Luca Di Lullo, Antonio Bellasi
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28600880/klotho-lacks-a-fgf23-independent-role-in-mineral-homeostasis
#7
Olena Andrukhova, Jessica Bayer, Christiane Schüler, Ute Zeitz, Sathish K Murali, Sibel Ada, Jose M Alvarez-Pez, Alina Smorodchenko, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating vitamin D hormone production and renal handling of minerals by signaling through a FGF receptor/αKlotho (Klotho) receptor complex. Whether Klotho has FGF23-independent effects on mineral homeostasis is a controversial issue. Here, we aimed to shed more light on this controversy by comparing male and female triple knockout mice with simultaneous deficiency in Fgf23 and Klotho and a nonfunctioning vitamin D receptor (VDR) (Fgf23/Klotho/VDR) with double (Fgf23/VDR, Klotho/VDR, and Fgf23/Klotho) and single Fgf23, Klotho and VDR mutants...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28600036/effects-of-liver-depression-and-psychological-stress-on-human-uterine-leiomyoma-cells-by-an-ar-camp-pka-signal-transduction-pathway
#8
Tian Xia, Shuang Li, Ruihong Ma, Sufen Guan, Jiacui Li, Hongqin Li, Hexin Zhang, Qiu Lin, Zhimei Zhao, Baojuan Wang
OBJECTIVE: Based on the emotional theory of Traditional Chinese Medicine, and combined with the modern medicine theory of psychological stress, a research model of human uterine leiomyoma cells (ULM) was cultured in vitro to determine the effectiveness of adrenergic receptor (AR) agonists in human ULM cell growth. In addition, we studied the functional influence of "liver depression and psychological stress theory" on fibroid formation by intervening in the AR-cAMP-PKA signaling pathway...
June 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28598150/high-yield-site-specific-conjugation-of-fibroblast-growth-factor-1-with-monomethylauristatin-e-via-cysteine-flanked-by-basic-residues
#9
Michal Lobocki, Malgorzata Zakrzewska, Anna Szlachcic, Mateusz Adam Krzyscik, Aleksandra Sokolowska-Wedzina, Jacek Otlewski
Site-specific conjugation is a leading trend in the development of protein conjugates, including antibody-drug conjugates (ADCs), suitable for targeted cancer therapy. Here, we present a very efficient strategy for specific attachment of a cytotoxic drug to fibroblast growth factor 1 (FGF1), a natural ligand of FGF receptors (FGFRs), which are overexpressed in several types of lung, breast and gastric cancers and are therefore an attractive molecular target. Recently we showed that FGF1 fused to monomethylauristatin E (vcMMAE) was highly cytotoxic to cells presenting FGFRs on their surface and could be used as a targeting agent alternative to an antibody...
June 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28595297/fgfr2-mutations-in-bent-bone-dysplasia-syndrome-activate-nucleolar-stress-and-perturb-cell-fate-determination
#10
Cynthia L Neben, Creighton T Tuzon, Xiaojing Mao, Fides D Lay, Amy E Merrill
Fibroblast growth factor (FGF) signaling promotes self-renewal in progenitor cells by encouraging proliferation and inhibiting cellular senescence. Yet, these beneficial effects can be hijacked by disease-causing mutations in FGF receptor (FGFR) during embryogenesis. By studying dominant FGFR2 mutations that are germline in Bent Bone Dysplasia Syndrome (BBDS), we reveal a mechanistic connection between FGFR2, ribosome biogenesis, and cellular stress that links cell fate determination to disease pathology. We previously showed that FGFR2 mutations in BBDS, which amplify nucleolar targeting of FGFR2, activate ribosomal DNA (rDNA) transcription and delay differentiation in osteoprogenitor cells and patient-derived bone...
June 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28589943/the-signalling-receptor-mcam-coordinates-apical-basal-polarity-and-planar-cell-polarity-during-morphogenesis
#11
Qian Gao, Junfeng Zhang, Xiumei Wang, Ying Liu, Rongqiao He, Xingfeng Liu, Fei Wang, Jing Feng, Dongling Yang, Zhaoqing Wang, Anming Meng, Xiyun Yan
The apical-basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28564583/fibroblast-growth-factors-fgfs-in-cancer-fgf-traps-as-a-new-therapeutic-approach
#12
REVIEW
Marco Presta, Paola Chiodelli, Arianna Giacomini, Marco Rusnati, Roberto Ronca
Originally characterized as angiogenic factors, fibroblast growth factors (FGFs) are pleiotropic factors that exert autocrine and paracrine functions on tumor and stromal cells. Thus, they may represent key players in the complex crosstalk among angiogenesis, inflammation, tumor growth, and drug resistance, all contributing to tumor progression. Given the multiple activities of FGFs, inhibitors of the FGF/FGFR system may act as "two compartment" targeting drugs able to exert a deep impact on the growth of FGF/FGFR-driven tumors...
May 28, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28560418/an-fgf8b-mimicking-peptide-with-potent-antiangiogenic-activity
#13
Xiaomian Lin, Li Song, Dan He, Xiangfeng Zeng, Jianzhang Wu, Wu Luo, Qi Yang, Jizhong Wang, Tianxiang Wang, Jialong Cai, Yanling Lin, Fubin Lai, Wentao Peng, Xiaoping Wu
Fibroblast growth factor (FGF) 8b interacts with its receptors and promotes angiogenesis in hormone‑dependent tumors. In the present study, we demonstrated that a short peptide, termed 8b‑13, which mimics part of the FGF8b structure, significantly inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) triggered by FGF8b using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT), flow cytometry and an in vitro scratch assay. In addition, the findings from western blotting and reverse transcription‑quantitative polymerase chain reaction revealed that 8b‑13 appeared to counteract the effects of FGF8b on the expression of cyclin D1, the activation of signaling cascades, and the expression of proangiogenic factors; these actions may be involved in the mechanism underlying the inhibitory effects of 8b‑13 on FGF8b‑induced HUVEC proliferation and migration...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28558791/receptor-tyrosine-kinases-play-a-significant-role-in-human-oligodendrocyte-inflammation-and-cell-death-associated-with-the-lyme-disease-bacterium-borrelia-burgdorferi
#14
Geetha Parthasarathy, Mario T Philipp
BACKGROUND: In previous studies, human oligodendrocytes were demonstrated to undergo apoptosis in the presence of Borrelia burgdorferi under an inflammatory milieu. Subsequently, we determined that the MEK/ERK pathway played a significant role in triggering downstream inflammation as well as apoptosis. However, the identity of receptors triggered by exposure to B. burgdorferi and initiating signaling events was unknown. METHODS: In this study, we explored the role of several TLR and EGFR/FGFR/PDGFR tyrosine kinase pathways in inducing inflammation in the presence of B...
May 30, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28556971/low-level-laser-therapy-780%C3%A2-nm-combined-with-collagen-sponge-scaffold-promotes-repair-of-rat-cranial-critical-size-defects-and-increases-tgf-%C3%AE-fgf-2-opg-rank-and-osteocalcin-expression
#15
Lana Sarita de Souza de Oliveira, Aurigena Antunes de Araújo, Raimundo Fernandes de Araújo Júnior, Carlos Augusto Galvão Barboza, Boniek Castillo Dutra Borges, José Sandro Pereira da Silva
The aim of this study was to evaluate the effect of collagen sponge scaffold (CSS) implantation associated with low-level laser therapy (LLLT) on repairing bone defects. A single 5-mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (n = 10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (CSS) alone (G1); defect treated with low-level laser therapy (LLLT) (wavelength 780 nm; total energy density 120 J/cm(2) ; power 50 mW) alone (G2); and CSS associated with LLLT treatment (G3)...
May 29, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28554854/hgf-induces-emt-in-non-small-cell-lung-cancer-through-the-hbvr-pathway
#16
Fang Liu, Shasha Song, Zhi Yi, Min Zhang, Jiali Li, Fang Yang, Hongtao Yin, Xiufeng Yu, Chao Guan, Ying Liu, Zizhen Liu, Jing Wang, Daling Zhu
The epithelial-to-mesenchymal transition (EMT) is a crucial event during non-small-cell lung cancer (NSCLC) invasion and metastasis. However, the mechanisms involved in NSCLC EMT have not been fully clarified. Hepatocyte growth factor (HGF) and human biliverdin reductase (hBVR) are reported to contribute to EMT in several diseases. Here, we show that compared with transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), and epidermal growth factor (EGF), HGF is an important cell factor for EMT in NSCLC cell lines A549 and H460...
May 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28552744/reduction-in-serum-fibroblast-growth-factor-21-after-gastric-bypass-is-related-to-changes-in-hepatic-fat-content
#17
Karen Fjeldborg, Steen B Pedersen, Holger J Møller, Bjørn Richelsen
BACKGROUND: Fibroblast growth factor 21 (FGF21) is elevated in obesity. OBJECTIVES: We investigated the circulating level of FGF21 and the expression of FGF21, beta-klotho (KLB), and FGF receptor 1 (FGFR1) in adipose tissue in relation to weight, fat distribution, and Roux-en-Y gastric bypass (RYGB)-induced weight loss. SETTING: The Department of Endocrinology at Aarhus University Hospital. METHODS: Thirty-one obese patients were enrolled...
April 7, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28552559/lineage-establishment-and-progression-within-the-inner-cell-mass-of-the-mouse-blastocyst-requires-fgfr1-and-fgfr2
#18
Minjung Kang, Vidur Garg, Anna-Katerina Hadjantonakis
Fibroblast growth factor 4 (FGF4) is the key signal driving specification of primitive endoderm (PrE) versus pluripotent epiblast (EPI) within the inner cell mass (ICM) of the mouse blastocyst. To gain insight into the receptor(s) responding to FGF4 within ICM cells, we combined single-cell-resolution quantitative imaging with single-cell transcriptomics of wild-type and Fgf receptor (Fgfr) mutant embryos. Despite the PrE-specific expression of FGFR2, it is FGFR1, expressed by all ICM cells, that is critical for establishment of a PrE identity...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28552557/distinct-requirements-for-fgfr1-and-fgfr2-in-primitive-endoderm-development-and-exit-from-pluripotency
#19
Andrei Molotkov, Pierre Mazot, J Richard Brewer, Ryan M Cinalli, Philippe Soriano
Activation of the FGF signaling pathway during preimplantation development of the mouse embryo is known to be essential for differentiation of the inner cell mass and the formation of the primitive endoderm (PrE). We now show using fluorescent reporter knockin lines that Fgfr1 is expressed in all cell populations of the blastocyst, while Fgfr2 expression becomes restricted to extraembryonic lineages, including the PrE. We further show that loss of both receptors prevents the development of the PrE and demonstrate that FGFR1 plays a more prominent role in this process than FGFR2...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28545562/the-inhibition-of-fgf-receptor-1-activity-mediates-sorafenib-antiproliferative-effects-in-human-malignant-pleural-mesothelioma-tumor-initiating-cells
#20
Alessandra Pattarozzi, Elisa Carra, Roberto E Favoni, Roberto Würth, Daniela Marubbi, Rosa Angela Filiberti, Luciano Mutti, Tullio Florio, Federica Barbieri, Antonio Daga
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. METHODS: TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro...
May 25, 2017: Stem Cell Research & Therapy
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