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https://www.readbyqxmd.com/read/29786918/novel-genes-and-insights-in-complete-asthma-remission
#1
Judith M Vonk, Maartje A E Nieuwenhuis, F Nicole Dijk, Anne Boudier, Valerie Siroux, Emmanuelle Bouzigon, Nicole Probst-Hensch, Medea Imboden, Dirk Keidel, Don Sin, Yohan Bossé, Ke Hao, Maarten van den Berge, Alen Faiz, Gerard H Koppelman, Dirkje S Postma
BACKGROUND: Asthma is a chronic respiratory disease without a cure, though there exists spontaneous remission. Genome wide association(GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVES: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years, and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR)...
May 22, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29763898/fgfr4-links-glucose-metabolism-and-chemotherapy-resistance-in-breast-cancer
#2
Min Xu, Shuzheng Chen, Weibin Yang, Xue Cheng, Yani Ye, Jianting Mao, Xulu Wu, Li Huang, Jiansong Ji
BACKGROUND/AIMS: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. METHODS: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR)...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29733511/lenvatinib-inhibits-angiogenesis-and-tumor-fibroblast-growth-factor-signaling-pathways-in-human-hepatocellular-carcinoma-models
#3
Masahiro Matsuki, Taisuke Hoshi, Yuji Yamamoto, Megumi Ikemori-Kawada, Yukinori Minoshima, Yasuhiro Funahashi, Junji Matsui
Unresectable hepatocellular carcinoma (uHCC) is one of the most lethal and prevalent cancers worldwide, and current systemic therapeutic options for uHCC are limited. Lenvatinib, a multiple receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), recently demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority to sorafenib in a phase 3 study of uHCC. Here, we investigated mechanisms underlying the antitumor activity of lenvatinib in preclinical HCC models...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29371290/the-phosphatase-ptprg-controls-fgfr1-activity-and-influences-sensitivity-to-fgfr-kinase-inhibitors
#4
Michal Kostas, Ellen Margrethe Haugsten, Yan Zhen, Vigdis Sorensen, Patrycja Szybowska, Elisa Fiorito, Susanne Lorenz, Gustavo Antonio de Souza, Antoni Wiedlocha, Jørgen Wesche
Recently, FGFR1 was found to be overexpressed in osteosarcoma and represents an important target for precision medicine. However, because targeted cancer therapy based on FGFR inhibitors has so far been less efficient than expected, a detailed understanding of the target is important. We have here applied proximity-dependent biotin labeling combined with label-free quantitative mass spectrometry to identify determinants of FGFR1 activity in an osteosarcoma cell line. Many known FGFR interactors were identified (e...
January 25, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29368794/amplification-of-frs2-in-atypical-lipomatous-tumour-well-differentiated-liposarcoma-and-dedifferentiated-liposarcoma-a-clinicopathological-and-genetic-study-of-146-cases
#5
Wenyi Jing, Ting Lan, Huijiao Chen, Zhang Zhang, Min Chen, Ran Peng, Xin He, Hongying Zhang
AIMS: Fibroblast growth factor receptor substrate 2 (FRS2) is located within the 12q13-15 band. The aim of this study was to evaluate the frequency of FRS2 amplification and its relationship with the clinicopathological features of atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL)/dedifferentiated liposarcoma (DDL). METHODS AND RESULTS: FRS2 and MDM2 fluorescence in situ hybridization (FISH) was performed on 146 tumours (70 ALT/WDLs and 76 DDLs)...
January 25, 2018: Histopathology
https://www.readbyqxmd.com/read/29360039/crk-proteins-transduce-fgf-signaling-to-promote-lens-fiber-cell-elongation
#6
Tamica N Collins, Yingyu Mao, Hongge Li, Michael Bouaziz, Angela Hong, Gen-Sheng Feng, Fen Wang, Lawrence A Quilliam, Lin Chen, Taeju Park, Tom Curran, Xin Zhang
Specific cell shapes are fundamental to the organization and function of multicellular organisms. Fibroblast Growth Factor (FGF) signaling induces the elongation of lens fiber cells during vertebrate lens development. Nonetheless, exactly how this extracellular FGF signal is transmitted to the cytoskeletal network has previously not been determined. Here, we show that the Crk family of adaptor proteins, Crk and Crkl, are required for mouse lens morphogenesis but not differentiation. Genetic ablation and epistasis experiments demonstrated that Crk and Crkl play overlapping roles downstream of FGF signaling in order to regulate lens fiber cell elongation...
January 23, 2018: ELife
https://www.readbyqxmd.com/read/29155277/neurotrophin-and-fgf-signaling-adapter-proteins-frs2-and-frs3-regulate-dentate-granule-cell-maturation-and-excitatory-synaptogenesis
#7
Sayan Nandi, Karina Alviña, Pablo J Lituma, Pablo E Castillo, Jean M Hébert
Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs...
January 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29098032/identification-of-mirna-and-genes-involving-in-osteosarcoma-by-comprehensive-analysis-of-microrna-and-copy-number-variation-data
#8
Tao Luo, Xiangli Yi, Wei Si
The aim of the present study was to understand the molecular mechanisms of osteosarcoma by comprehensive analysis of microRNA (miRNA/miR) and copy number variation (CNV) microarray data. Microarray data (GSE65071 and GSE33153) were downloaded from the Gene Expression Omnibus. In GSE65071, differentially expressed miRNAs between the osteosarcoma and control groups were calculated by the Limma package. Target genes of differentially expressed miRNAs were identified by the starBase database. For GSE33153, PennCNV software was used to perform the copy number variation (CNV) analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/28947594/mir-339-inhibits-proliferation-of-pulmonary-artery-smooth-muscle-cell-by-targeting-fgf-signaling
#9
Jidong Chen, Xiaolei Cui, Li Li, Junle Qu, J Usha Raj, Deming Gou
Pulmonary artery hypertension (PAH) is a fatal disorder. Recent studies suggest that microRNA (miRNA) plays an important role in regulating proliferation of pulmonary artery smooth muscle cells (PASMC), which underlies the pathology of PAH However, the exact mechanism of action of miRNAs remains elusive. In this study, we found that miR-339 was highly expressed in the cardiovascular system and was downregulated by a group of cytokines and growth factors, especially PDGF-BB and FGF2. Functional analyses revealed that miR-339 can inhibit proliferation of PASMC Also, miR-339 inhibited FGF2-induced proliferation, but had no effect on proliferation induced by PDGF-BB The fibroblast growth factor receptor substrate 2 (FRS2) was identified as a potential direct target of miR-339...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28895643/thyroid-hormone-induced-expression-of-the-hepatic-scaffold-proteins-sestrin2-%C3%AE-klotho-and-frs2%C3%AE-in-relation-to-fgf21-ampk-signaling
#10
Luis A Videla, Romina Vargas, Barbara Riquelme, Javier Fernández, Virginia Fernández
Thyroid hormone (3,3',5-triiodothyronine, T3 ) accelerates energy metabolism in the liver through mechanisms involving upregulation of AMP-activated protein kinase (AMPK). This study aims to assess the influence of T3 on the expression of the scaffold proteins β-Klotho, fibroblast growth factor receptor substrate 2α (FRS2α), and Sestrin2 in relation to FGF21-AMPK signaling. Male Sprague-Dawley rats were given 0.1 mg T3 /kg or hormone vehicle (controls) and studies were done 24 h after treatment. These include measurements of the mRNA expression (qPCR) of hepatic β-Klotho, FGF21, FGF21 receptor-1 (FGFR1), extracellular-signal-regulated kinase 1/2 (ERK1/2), FRS2α, ribosomal S6 kinase-1 (RSK1), liver kinase B1 (LKB1), AMPK, and Sestrin2...
March 2018: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28829507/microrna-613-attenuates-the-proliferation-migration-and-invasion-of-wilms-tumor-via-targeting-frs2
#11
H-F Wang, Y-Y Zhang, H-W Zhuang, M Xu
OBJECTIVE: Wilms' tumor is the most common malignant tumor in children worldwide. Considering the poor therapeutic effect on Wilms' tumor, we determined the effects of microRNA-613 on cell proliferation and metastasis in vitro, providing therapeutic targets for the treatment of Wilms' tumor. PATIENTS AND METHODS: Quantitative real-time PCR (qRT-PCR) was employed to identify the expression level of miR-613. CCK8 and colony formation assays were incorporated to assess cell viability and proliferation capacity...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28771231/fgfr1-is-critical-for-the-anti-endothelial-mesenchymal-transition-effect-of-n-acetyl-seryl-aspartyl-lysyl-proline-via-induction-of-the-map4k4-pathway
#12
Jinpeng Li, Sen Shi, Swayam Prakash Srivastava, Munehiro Kitada, Takako Nagai, Kyoko Nitta, Miyuki Kohno, Keizo Kanasaki, Daisuke Koya
Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis, and we have reported that the anti-EndMT effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is associated with restoring expression of diabetes-suppressed fibroblast growth factor receptor (FGFR), the key anti-EndMT molecule. FGFR1 is the key inhibitor of EndMT via the suppression of the transforming growth factor β (TGFβ) signaling pathway, and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibits integrin β1, a key factor in activating TGFβ signaling and EndMT...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28558797/expression-of-signaling-adaptor-proteins-predicts-poor-prognosis-in-pancreatic-ductal-adenocarcinoma
#13
Lili Wang, Junliang Lu, Huanwen Wu, Li Wang, Xiaolong Liang, Zhiyong Liang, Tonghua Liu
BACKGROUND: Adaptor proteins bridge the gap between cell surface receptors and their downstream signaling elements. The clinicopathological and prognostic values of adaptor proteins remain poorly understood. The purpose of the present study was to explore the expression and prognostic value of three adaptor proteins: GRB2-associated binding protein 2 (GAB2), CRK-like protein (CRKL) and fibroblast growth factor receptor substrate 2 (FRS2) in pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of GAB2, CRKL, and FRS2 in 77 formalin fixed paraffin embedded (FFPE) samples from 77 PDAC patients, along with three paired fresh PDAC and matched normal tissues from 3 PDAC patients was analyzed by immunohistochemistry and western blot, respectively...
May 30, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28483978/fgf-dependent-context-driven-role-for-frs-adapters-in-the-early-telencephalon
#14
Sayan Nandi, Grigoriy Gutin, Christopher A Blackwood, Nachiket G Kamatkar, Kyung W Lee, Gordon Fishell, Fen Wang, Mitchell Goldfarb, Jean M Hébert
FGF signaling, an important component of intercellular communication, is required in many tissues throughout development to promote diverse cellular processes. Whether FGF receptors (FGFRs) accomplish such varied tasks in part by activating different intracellular transducers in different contexts remains unclear. Here, we used the developing mouse telencephalon as an example to study the role of the FRS adapters FRS2 and FRS3 in mediating the functions of FGFRs. Using tissue-specific and germline mutants, we examined the requirement of Frs genes in two FGFR-dependent processes...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28473845/pancreatic-islet-protein-complexes-and-their-dysregulation-in-type-2-diabetes
#15
Helle Krogh Pedersen, Valborg Gudmundsdottir, Søren Brunak
Type 2 diabetes (T2D) is a complex disease that involves multiple genes. Numerous risk loci have already been associated with T2D, although many susceptibility genes remain to be identified given heritability estimates. Systems biology approaches hold potential for discovering novel T2D genes by considering their biological context, such as tissue-specific protein interaction partners. Pancreatic islets are a key T2D tissue and many of the known genetic risk variants lead to impaired islet function, hence a better understanding of the islet-specific dysregulation in the disease-state is essential to unveil the full potential of person-specific profiles...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#16
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#17
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077787/androgen-suppresses-protein-kinase-d1-expression-through-fibroblast-growth-factor-receptor-substrate-2-in-prostate-cancer-cells
#18
Liyong Zhang, Zhenlong Zhao, Shuping Xu, Manuj Tandon, Courtney R LaValle, Fan Deng, Q Jane Wang
In prostate cancer, androgen/androgen receptor (AR) and their downstream targets play key roles in all stages of disease progression. The protein kinase D (PKD) family, particularly PKD1, has been implicated in prostate cancer biology. Here, we examined the cross-regulation of PKD1 by androgen signaling in prostate cancer cells. Our data showed that the transcription of PKD1 was repressed by androgen in androgen-sensitive prostate cancer cells. Steroid depletion caused up regulation of PKD1 transcript and protein, an effect that was reversed by the AR agonist R1881 in a time- and concentration-dependent manner, thus identifying PKD1 as a novel androgen-repressed gene...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27811184/coupling-an-eml4-alk-centric-interactome-with-rna-interference-identifies-sensitizers-to-alk-inhibitors
#19
Guolin Zhang, Hannah Scarborough, Jihye Kim, Andrii I Rozhok, Yian Ann Chen, Xiaohui Zhang, Lanxi Song, Yun Bai, Bin Fang, Richard Z Liu, John Koomen, Aik Choon Tan, James Degregori, Eric B Haura
Patients with lung cancers harboring anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with ALK inhibitors, but acquired resistance inevitably arises. A better understanding of proximal ALK signaling mechanisms may identify sensitizers to ALK inhibitors that disrupt the balance between prosurvival and proapoptotic effector signals. Using affinity purification coupled with mass spectrometry in an ALK fusion lung cancer cell line (H3122), we generated an ALK signaling network and investigated signaling activity using tyrosine phosphoproteomics...
October 18, 2016: Science Signaling
https://www.readbyqxmd.com/read/27664399/in-silico-prediction-and-in-vitro-and-in-vivo-validation-of-acaricide-fluazuron-as-a-potential-inhibitor-of-fgfr3-and-a-candidate-anticancer-drug-for-bladder-carcinoma
#20
Kunbin Ke, Hongjian Li, Hong Yao, Xi-Nan Shi, Chao Dong, Ying Zhu, Xu Liu, Ling Li, Kwong-Sak Leung, Man-Hon Wong, Xiao-Dong Liu, Hsiang-Fu Kung, Marie Chia-Mi Lin
Bladder carcinoma (BC) is the ninth most common cause of cancer worldwide. Surgical resection and conventional chemotherapy and radiotherapy will ultimately fail due to tumor recurrence and resistance. Thus, the development of novel treatment is urgently needed. Fibroblast growth factor receptor 3 (FGFR3) is an important and well-established target for BC treatment. In this study, we utilized the free and open-source protein-ligand docking software idock to prospectively identify potential inhibitors of FGFR3 from 3,167 worldwide approved small-molecule drugs using a repositioning strategy...
April 2017: Chemical Biology & Drug Design
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