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https://www.readbyqxmd.com/read/29470991/modeling-factors-that-regulate-cell-cooperativity-in-the-zebrafish-posterior-lateral-line-primordium
#1
Leif Zinn-Björkman, Frederick R Adler
Collective cell migration is an integral part of organismal development. We consider migration of the zebrafish primordium during development of the posterior lateral line, a sensory system that detects water movement patterns. Experiments have shown that the chemokine ligand CXCL12a and its receptors CXCR4b and CXCR7b are key players for driving migration of the primordium, while FGF signaling helps maintain cohesion. In this work, we formulate a mathematical model of a laser ablated primordium separated into two smaller cell collectives: a leading collective that responds to local CXCL12a levels and a trailing collective that migrates up a local FGF gradient...
February 19, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29468415/the-ileal-fgf15-19-to-hepatic-fgfr4-axis-regulates-liver-regeneration-after-partial-hepatectomy-in-mice
#2
Qiang Li, Qiang Zhao, Chuanzhao Zhang, Peng Zhang, Anbin Hu, Longjuan Zhang, Paul M Schroder, Yi Ma, Zhiyong Guo, Xiaofeng Zhu, Xiaoshun He
Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling...
February 22, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29467286/viral-insulin-like-peptides-activate-human-insulin-and-igf-1-receptor-signaling-a-paradigm-shift-for-host-microbe-interactions
#3
Emrah Altindis, Weikang Cai, Masaji Sakaguchi, Fa Zhang, Wang GuoXiao, Fa Liu, Pierre De Meyts, Vasily Gelfanov, Hui Pan, Richard DiMarchi, C Ronald Kahn
Viruses are the most abundant biological entities and carry a wide variety of genetic material, including the ability to encode host-like proteins. Here we show that viruses carry sequences with significant homology to several human peptide hormones including insulin, insulin-like growth factors (IGF)-1 and -2, FGF-19 and -21, endothelin-1, inhibin, adiponectin, and resistin. Among the strongest homologies were those for four viral insulin/IGF-1-like peptides (VILPs), each encoded by a different member of the family Iridoviridae VILPs show up to 50% homology to human insulin/IGF-1, contain all critical cysteine residues, and are predicted to form similar 3D structures...
February 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29459310/regulation-of-vitamin-d-metabolism-following-disruption-of-the-microbiota-using-broad-spectrum-antibiotics
#4
Stephanie A Bora, Mary J Kennett, Philip B Smith, Andrew D Patterson, Margherita T Cantorna
Vitamin D, 25hydroxyvitamin D (25D), and 24,25dihydroxyvitamin D (24,25D) were measured before and after broad spectrum antibiotic (Abx) treatment for 2 wks. Abx treatments increased 25D and 24,25D levels suggesting that the microbiota or Abx were altering vitamin D metabolism. Increased 25D, but not 24,25D, following Abx treatments were found to be dependent on toll like receptor signaling. Conversely, the effects of Abx on 24,25D levels required that the vitamin D receptor (VDR) be expressed in tissues outside of the hematopoietic system (kidney) and not the immune system...
February 2, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29453876/prognostic-importance-of-fgf2-and-fgfr1-expression-for-patients-affected-by-ameloblastoma
#5
Felipe Paiva Fonseca, Bernar Monteiro Benites, Ciro Dantas Soares, Thayná Melo de Lima Morais, Gleyson Kleber do Amaral-Silva, Oslei Paes de Almeida, Fernando Augusto Soares, Eduardo Rodrigues Fregnani
BACKGROUND: Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have been investigated in different human neoplasms and were shown to play important roles in the pathogenesis of these diseases; however, very few is known regarding their prognostic importance in the context of ameloblastoma. Therefore, the aim of this study is to investigate if the expression of FGF2 and FGFR1 is associated with ameloblastoma clinical behavior. METHODS: Fifty-eight cases of ameloblastoma arranged in tissue microarray were submitted to immunohistochemistry against FGF2 and FGFR1...
February 17, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29444487/paracrine-fibroblast-growth-factor-initiates-oncogenic-synergy-with-epithelial-fgfr-src-transformation-in-prostate-tumor-progression
#6
Qianjin Li, Lishann Ingram, Sungjin Kim, Zanna Beharry, Jonathan A Cooper, Houjian Cai
Cross talk of stromal-epithelial cells plays an essential role in both normal development and tumor initiation and progression. Fibroblast growth factor (FGF)-FGF receptor (FGFR)-Src kinase axis is one of the major signal transduction pathways to mediate this cross talk. Numerous genomic studies have demonstrated that expression levels of FGFR/Src are deregulated in a variety of cancers including prostate cancer; however, the role that paracrine FGF (from stromal cells) plays in dysregulated expression of epithelial FGFRs/Src and tumor progression in vivo is not well evaluated...
February 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29436393/therapeutically-targeting-tumor-microenvironment-mediated-drug-resistance-in-estrogen-receptor-positive-breast-cancer
#7
Kevin Shee, Wei Yang, John W Hinds, Riley A Hampsch, Frederick S Varn, Nicole A Traphagen, Kishan Patel, Chao Cheng, Nicole P Jenkins, Arminja N Kettenbach, Eugene Demidenko, Philip Owens, Anthony C Faber, Todd R Golub, Ravid Straussman, Todd W Miller
Drug resistance to approved systemic therapies in estrogen receptor-positive (ER+) breast cancer remains common. We hypothesized that factors present in the human tumor microenvironment (TME) drive drug resistance. Screening of a library of recombinant secreted microenvironmental proteins revealed fibroblast growth factor 2 (FGF2) as a potent mediator of resistance to anti-estrogens, mTORC1 inhibition, and phosphatidylinositol 3-kinase inhibition in ER+ breast cancer. Phosphoproteomic analyses identified ERK1/2 as a major output of FGF2 signaling via FGF receptors (FGFRs), with consequent up-regulation of Cyclin D1 and down-regulation of Bim as mediators of drug resistance...
February 7, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29433850/lenvatinib-versus-sorafenib-in-first-line-treatment-of-patients-with-unresectable-hepatocellular-carcinoma-a-randomised-phase-3-non-inferiority-trial
#8
Masatoshi Kudo, Richard S Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Fabio Piscaglia, Ari Baron, Joong-Won Park, Guohong Han, Jacek Jassem, Jean Frederic Blanc, Arndt Vogel, Dmitry Komov, T R Jeffry Evans, Carlos Lopez, Corina Dutcus, Matthew Guo, Kenichi Saito, Silvija Kraljevic, Toshiyuki Tamai, Min Ren, Ann-Lii Cheng
BACKGROUND: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. METHODS: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions...
February 9, 2018: Lancet
https://www.readbyqxmd.com/read/29425341/fibroblast-growth-factor-23-is-induced-by-an-activated-renin-angiotensin-aldosterone-system-in-cardiac-myocytes-and-promotes-the-pro-fibrotic-crosstalk-between-cardiac-myocytes-and-fibroblasts
#9
Maren Leifheit-Nestler, Felix Kirchhoff, Julia Nespor, Beatrice Richter, Birga Soetje, Michael Klintschar, Joerg Heineke, Dieter Haffner
Background: Fibroblast growth factor 23 (FGF23) is discussed as a new biomarker of cardiac hypertrophy and mortality in patients with and without chronic kidney disease (CKD). We previously demonstrated that FGF23 is expressed by cardiac myocytes, enhanced in CKD and induces cardiac hypertrophy via activation of FGF receptor 4 independent of its co-receptor klotho. The impact of FGF23 on cardiac fibrosis is largely unknown. Methods: By conducting a retrospective case-control study including myocardial autopsy samples from 24 patients with end-stage CKD and in vitro studies in cardiac fibroblasts and myocytes, we investigated the pro-fibrotic properties of FGF23...
February 7, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29420662/generation-of-high-affinity-internalizing-anti-fgfr2-single-chain-variable-antibody-fragment-fused-with-fc-for-targeting-gastrointestinal-cancers
#10
Aleksandra Borek, Aleksandra Sokolowska-Wedzina, Grzegorz Chodaczek, Jacek Otlewski
Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2)...
2018: PloS One
https://www.readbyqxmd.com/read/29417581/vegf-fgf-2-and-tgf%C3%AE-expression-in-the-normal-and-regenerating-epidermis-of-geckos-implications-for-epidermal-homeostasis-and-wound-healing-in-reptiles
#11
Noeline Subramaniam, James J Petrik, Matthew K Vickaryous
The skin is a bilayered organ that serves as a key barrier between an organism and its environment. In addition to protecting against microbial invasion, physical trauma and environmental damage, skin participates in maintaining homeostasis. Skin is also capable of spontaneous self-repair following injury. These functions are mediated by numerous pleiotrophic growth factors, including members of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and transforming growth factor β (TGFβ) families...
February 8, 2018: Journal of Anatomy
https://www.readbyqxmd.com/read/29409758/postprandial-regulation-of-natriuretic-peptides-in-vivo-and-of-their-receptors-by-fatty-acids-in-adipocytes-in-vitro
#12
Andreas Schmid, Jens Albrecht, Judith Brock, Maria Koukou, Efthymia Arapogianni, Andreas Schäffler, Thomas Karrasch
BACKGROUND AND AIM: Natriuretic peptides (NPs) and their receptors gain attention regarding adipocyte function. It was the aim to investigate the expression of natriuretic peptide receptors NPR-A, NPR-B, NPR-C during adipocyte differentiation (AD), upon stimulation with fatty acids (FA), and in murine and human adipose tissue depots (AT) of patients undergoing bariatric surgery (n = 44). PATIENTS, MATERIAL AND METHODS: The postprandial regulation of NT-proANP and NT-proBNP levels was measured by ELISA and was studied in two cohorts of healthy individuals undergoing an oral glucose tolerance test (OGTT) (n = 100) and an oral lipid tolerance test (OLTT) (n = 100)...
January 30, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29382567/fibroblast-growth-factor-type-1-receptor-stimulation-of-t-type-ca2-channels-in-sensory-neurons-requires-the-phosphatidylinositol-3-kinase-and-protein-kinase-a-pathways-independently-of-akt
#13
Weibing Si, Yuan Zhang, Kun Chen, Dan Hu, Zhiyuan Qian, Shan Gong, Hua Li, Yuefeng Hao, Jin Tao
Fibroblast growth factor-23 (FGF-23) secreted by osteocytes is known as a circulating factor that is essential for phosphate homeostasis. Recent studies have implicated FGF-23 in the nociceptive signalling of peripheral sensory neurons. However, the relevant mechanisms underlying this effect are not known. In this study, we determine the role of FGF-23 in regulating T-type Ca2+ channels (T-type channels) in small-diameter dorsal root ganglion (DRG) neurons in mice. Our results show that FGF-23 increases T-type channel currents in a concentration-dependent manner...
January 27, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29372690/association-of-single-nucleotide-polymorphisms-in-fgf-ras-map-signalling-cascade-with-breast-cancer-susceptibility
#14
Zuzana Dankova, Pavol Zubor, Marian Grendar, Andrea Kapinova, Katarina Zelinova, Mariana Jagelkova, Alexandra Gondova, Karol Dokus, Michal Kalman, Zora Lasabova, Jan Danko
The fibroblast growth factor receptors (FGFRs) and Ras/mitogen activated protein (RAS/MAP) signalling cascades are the main molecular pathways involved in breast carcinogenesis. This study aims to determine the association between FGF10 (rs4415084 C>T), FGFR2 (rs2981582 C>T) and MAP3K1 (rs889312 A>C) gene polymorphisms and breast cancer, to analyse the discriminative ability of each SNP and to test the accuracy of the predictive breast cancer risk model which includes all SNPs. We conducted a case-control study of 170 women (57...
December 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29365460/significance-of-growth-factors-igf-1-fgf-b-pdgf-aa-pro-inflammatory-cytokines-and-cytokine-soluble-receptors-in-gouty-patients-with-insulin-resistance
#15
Natalia Kushnarenko, Tatyana Medvedeva, Anatoly Govorin, Kirill Kushnarenko
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29342870/biomarkers-of-progression-after-hiv-acute-early-infection-nothing-compares-to-cd4%C3%A2-%C2%BA-t-cell-count
#16
Gabriela Turk, Yanina Ghiglione, Macarena Hormanstorfer, Natalia Laufer, Romina Coloccini, Jimena Salido, César Trifone, María Julia Ruiz, Juliana Falivene, María Pía Holgado, María Paula Caruso, María Inés Figueroa, Horacio Salomón, Luis D Giavedoni, María de Los Ángeles Pando, María Magdalena Gherardi, Roberto Daniel Rabinovich, Pedro A Pury, Omar Sued
Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29342138/%C3%AE-klotho-is-a-non-enzymatic-molecular-scaffold-for-fgf23-hormone-signalling
#17
Gaozhi Chen, Yang Liu, Regina Goetz, Lili Fu, Seetharaman Jayaraman, Ming-Chang Hu, Orson W Moe, Guang Liang, Xiaokun Li, Moosa Mohammadi
The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of α-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, α-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342135/structures-of-%C3%AE-klotho-reveal-a-zip-code-like-mechanism-for-endocrine-fgf-signalling
#18
Sangwon Lee, Jungyuen Choi, Jyotidarsini Mohanty, Leiliane P Sousa, Francisco Tome, Els Pardon, Jan Steyaert, Mark A Lemmon, Irit Lax, Joseph Schlessinger
Canonical fibroblast growth factors (FGFs) activate FGF receptors (FGFRs) through paracrine or autocrine mechanisms in a process that requires cooperation with heparan sulfate proteoglycans, which function as co-receptors for FGFR activation. By contrast, endocrine FGFs (FGF19, FGF21 and FGF23) are circulating hormones that regulate critical metabolic processes in a variety of tissues. FGF19 regulates bile acid synthesis and lipogenesis, whereas FGF21 stimulates insulin sensitivity, energy expenditure and weight loss...
January 25, 2018: Nature
https://www.readbyqxmd.com/read/29337115/purification-of-gfr%C3%AE-1-and-gfr%C3%AE-1-spermatogonial-stem-cells-reveals-a%C3%A2-niche-dependent-mechanism-for-fate-determination
#19
Alina Garbuzov, Matthew F Pech, Kazuteru Hasegawa, Meena Sukhwani, Ruixuan J Zhang, Kyle E Orwig, Steven E Artandi
Undifferentiated spermatogonia comprise a pool of stem cells and progenitor cells that show heterogeneous expression of markers, including the cell surface receptor GFRα1. Technical challenges in isolation of GFRα1+ versus GFRα1- undifferentiated spermatogonia have precluded the comparative molecular characterization of these subpopulations and their functional evaluation as stem cells. Here, we develop a method to purify these subpopulations by fluorescence-activated cell sorting and show that GFRα1+ and GFRα1- undifferentiated spermatogonia both demonstrate elevated transplantation activity, while differing principally in receptor tyrosine kinase signaling and cell cycle...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#20
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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