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FGFR1

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https://www.readbyqxmd.com/read/28087897/fgfr1-analyses-in-four-patients-with-hypogonadotropic-hypogonadism-with-split-hand-foot-malformation-implications-for-the-promoter-region
#1
Kohnosuke Ohtaka, Yasuko Fujisawa, Fumio Takada, Yukihiro Hasegawa, Tatsuya Miyoshi, Tomonobu Hasegawa, Hideaki Miyoshi, Hiraku Kameda, Misuzu Kurokawa Seo, Maki Fukami, Tsutomu Ogata
Heterozygous loss-of-function mutations of FGFR1 cause various disorders including hypogonadotropic hypogonadism with split-hand/foot malformation (HH-SHFM). We examined FGFR1 in four Japanese patients with HH-SHFM (cases 1-4) and the mother of case 4 with HH only. Cases 1 and 2 had heterozygous loss-of-function mutations with no dominant negative effect [c.289G>A, p.(G97S); and c.2231G>C, p.(R744T)], and case 3 had a splice donor site mutation [c.1663+1G>T]. Notably, case 4 had a maternally inherited 8,312 bp microdeletion that involved non-coding exon 1U and impaired FGFR1 expression...
January 13, 2017: Human Mutation
https://www.readbyqxmd.com/read/28076758/polysaccharides-from-ganoderma-lucidum-promote-cognitive-function-and%C3%A2-neural-progenitor-proliferation-in-mouse-model-of-alzheimer-s-disease
#2
Shichao Huang, Jianxin Mao, Kan Ding, Yue Zhou, Xianglu Zeng, Wenjuan Yang, Peipei Wang, Cun Zhao, Jian Yao, Peng Xia, Gang Pei
Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28069708/ubiquitylation-dependent-oligomerization-regulates-activity-of-nedd4-ligases
#3
Ilan Attali, William Sam Tobelaim, Avinash Persaud, Khatereh Motamedchaboki, Kobi J Simpson-Lavy, Bayan Mashahreh, Olga Levin-Kravets, Tal Keren-Kaplan, Inbar Pilzer, Martin Kupiec, Reuven Wiener, Dieter A Wolf, Daniela Rotin, Gali Prag
Ubiquitylation controls protein function and degradation. Therefore, ubiquitin ligases need to be tightly controlled. We discovered an evolutionarily conserved allosteric restraint mechanism for Nedd4 ligases and demonstrated its function with diverse substrates: the yeast soluble proteins Rpn10 and Rvs167, and the human receptor tyrosine kinase FGFR1 and cardiac IKS potassium channel. We found that a potential trimerization interface is structurally blocked by the HECT domain α1-helix, which further undergoes ubiquitylation on a conserved lysine residue...
January 9, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28060197/identical-twins-discordant-for-metopic-craniosynostosis-evidence-of-epigenetic-influences
#4
Suresh N Magge, Kendall Snyder, Aparna Sajja, Tiffani A DeFreitas, Sean E Hofherr, Richard E Broth, Robert F Keating, Gary F Rogers
Craniosynostosis, or premature fusion of the cranial sutures, occurs in approximately 1 in 2500 live births. The genetic causes and molecular basis of these disorders have greatly expanded over the last 2 decades, with numerous causative and contributory mutations having been identified. The role of fibroblast growth factor receptor (FGFR) mutations in the etiology of certain eponymous forms of craniosynostosis is now well elucidated; the most common syndromes associated with craniosynostosis are Pfeifer (FGFR1, FGFR2), Apert (FGFR2), Crouzon (FGFR2), Saethre-Chotzen (TWIST1), Jackson-Weiss (FGFR2), Greig (GL13), and Muenke (FGFR3) syndromes...
January 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28056982/different-clinical-significance-of-fgfr1-4-expression-between-diffuse-type-and-intestinal-type-gastric-cancer
#5
Mikito Inokuchi, Hideaki Murase, Sho Otsuki, Tatsuyuki Kawano, Kazuyuki Kojima
BACKGROUND: Receptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1-4 expression separately in DGC and IGC. METHODS: Tumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution...
January 5, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28052020/the-rna-binding-protein-esrp1-promotes-human-colorectal-cancer-progression
#6
Sharmila Fagoonee, Gabriele Picco, Francesca Orso, Arrigo Arrigoni, Dario L Longo, Marco Forni, Irene Scarfò, Adele Cassenti, Roberto Piva, Paola Cassoni, Lorenzo Silengo, Emanuela Tolosano, Silvio Aime, Daniela Taverna, Pier Paolo Pandolfi, Mara Brancaccio, Enzo Medico, Fiorella Altruda
Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RNA binding protein that controls several key cellular processes, like alternative splicing and translation. Previous studies have demonstrated a tumor suppressor role for this protein. Recently, however, a pro-metastatic function of ESRP1 has been reported. We thus aimed at clarifying the role of ESRP1 in Colorectal Cancer (CRC) by performing loss- and gain-of-function studies, and evaluating tumorigenesis and malignancy with in vitro and in vivo approaches...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049184/binding-of-human-recombinant-mutant-soluble-ectodomain-of-fgfr2iiic-to-c-subtype-of-fgfrs-implications-for-anticancer-activity
#7
Zhong Liu, Ge Liu, Guang-Lin Zhang, Jun Li, Yan-Qing He, Shu-Shu Zhang, Yi Wang, Wei-Yi He, Guo-Hua Cheng, Xuesong Yang, Jun Xu, Ju Wang
FGFRs are considered essential targets for cancer therapy. We previously reported that msFGFR2c, a Ser252Trp mutant soluble ectodomain of FGFR2IIIc, inhibited tumor growth by blocking FGF signaling pathway. However, the underlying molecular mechanism is still obscure. In this study, we reported that msFGFR2c but not wild-type soluble ectodomain of FGFR2IIIc (wsFGFR2c) could selectively bind to c subtype of FGFRs in the presence of FGF-2. Thermodynamic analysis demonstrated that msFGFR2c bound to wsFGFR2c in the presence of FGF-2 with a K value of 6...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028030/myeloid-neoplasms-with-eosinophilia
#8
Andreas Reiter, Jason Gotlib
Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of myeloid neoplasms with eosinophilia. The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, 'Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2' In addition to myeloproliferative neoplasms (MPN), these patients can present with myelodysplastic syndrome/MPN, as well as de novo or secondary mixed phenotype acute leukemias/lymphomas...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28025079/%C3%AE-iii-tubulin-overexpression-is-linked-to-agressive-tumor-features-and-genetic-instability-in-urinary-bladder-cancer
#9
Andrea Hinsch, Aref Chaker, Christian Burdelski, Christina Koop, Maria Christina Tsourlakis, Stefan Steurer, Michael Rink, Till Simon Eichenauer, Waldemar Wilczak, Corinna Wittmer, Margit Fisch, Ronald Simon, Guido Sauter, Franziska Büschek, Till Clauditz, Sarah Minner, Frank Jacobsen
Development of genetic instability is a hallmark of tumor progression. Type III ß-tubulin (TUBB3) is a component of microtubules involved in chromosome segregation. Its overexpression has been linked to adverse features of urinary bladder cancer. To investigate the role of TUBB3 for development of genetic instability, we compared TUBB3 expression with histopathological features and surrogate markers of genetic instability and tumor aggressiveness, copy number changes of HER2, TOP2A, CCND1, RAF1, and FGFR1, nuclear accumulation of p53, and cell proliferation, in a tissue microarray with >700 bladder cancers...
December 23, 2016: Human Pathology
https://www.readbyqxmd.com/read/28008864/idiopathic-hypogonadothropic-hypogonadism-due-to-novel-fgfr1-mutations
#10
Gamze Akkuş, Damla Kotan, Erdem Durmaz, Eda Mengen, İhsan Turan, Ayça Ulubay, Fatih Gürbüz, Bilgin Yüksel, Tamer Tetiker, Ali Kemal Topaloğlu
OBJECTIVE: Underlying genetic etiology of Hypogonadothropic Hypogonadism (HH) is heterogenous. Fibroblast growth factor signaling is pivotal in the ontogeny of GnRH neurons. Loss of function mutations inFGFR1 gene cause variable hypogonadothropic hypogonadism phenotype encompassing pubertal delay to IHH or KS. As FGFR1 mutations are common, recognizing mutations and associated phenotypes may enhance clinical management. METHODS: Using a candidate gene approach we screened 52 IHH/KS patients...
December 23, 2016: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28008744/programmed-cell-death-ligand-1-pd-l1-expression-and-fibroblast-growth-factor-receptor-1-fgfr1-amplification-in-stage-iii-iv-lung-squamous-cell-carcinoma-sqc
#11
Qinxiang Guo, Yu Sun, Sifan Yu, Hua Bai, Jun Zhao, Minglei Zhuo, Jie Wang
BACKGROUND: This study was conducted to explore programmed cell death-ligand-1 (PD-L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage IIIB/IV lung squamous cell carcinoma (SQC). Correlations between PD-L1 and FGFR1, and with clinicopathological characteristics, efficacy of platinum-based chemotherapy, and prognosis were analyzed. METHODS: One hundred and twenty-eight consecutive stage III/IV SQC patients were enrolled in this study from 2009 to 2014...
December 23, 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/28008155/combination-treatment-of-prostate-cancer-with-fgf-receptor-and-akt-kinase-inhibitors
#12
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/28004110/effects-of-the-regulation-of-polysialyltransferase-st8siaii-on-the-invasiveness-and-metastasis-of-small-cell-lung-cancer-cells
#13
Liang Gong, Xiangdong Zhou, Jingxiang Yang, Yongyuan Jiang, Heping Yang
Invasiveness and metastasis may seriously affect the prognosis of small cell lung cancer (SCLC). In the present study, we analyzed the effects and inherent mechanisms of action of polysialic acid-modified neural cell adhesion molecule (NCAM) on the invasive and metastatic potential of SCLC. Gene transfection and short hairpin RNA (shRNA) interference were used to enhance or inhibit, respectively, the expression of polysialyltransferase ST8SiaII in the SCLC cell line H446. We studied in vitro positive or negative changes in the invasive and metastatic potential of the SCLC cells as well as the changes in expression of genes related to signaling molecules and metastasis...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27993329/an-mrna-gene-expression-based-signature-to-identify-fgfr1-amplified-estrogen-receptor-positive-breast-tumors
#14
Jingqin Luo, Shuzhen Liu, Samuel Leung, Alejandro A Gru, Yu Tao, Jeremy Hoog, Julie Ho, Sherri R Davies, D Craig Allred, Andrea L Salavaggione, Jacqueline Snider, Elaine R Mardis, Torsten O Nielsen, Matthew J Ellis
Fibroblast growth factor receptor 1 (FGFR1) amplification drives poor prognosis and is an emerging therapeutic target. We sought to construct a multigene mRNA expression signature to efficiently identify FGFR1-amplified estrogen receptor-positive (ER(+)) breast tumors. Five independent breast tumor series were analyzed. Genes discriminative for FGFR1 amplification were screened transcriptome-wide by receiver operating characteristic analyses. The METABRIC series was leveraged to construct/evaluate four approaches to signature composition...
January 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27992319/therapeutics-targeting-fgf-signaling-network-in-human-diseases
#15
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/27989801/molecular-checkpoint-decisions-made-by-subverted-vascular-niche-transform-indolent-tumor-cells-into-chemoresistant-cancer-stem-cells
#16
Zhongwei Cao, Joseph M Scandura, Giorgio G Inghirami, Koji Shido, Bi-Sen Ding, Shahin Rafii
Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R)...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27988457/in-vitro-and-in-vivo-activity-of-lucitanib-in-fgfr1-2-amplified-or-mutated-cancer-models
#17
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/27976968/a-fgfr1-inhibitor-patent-review-progress-since-2010
#18
Tao Yu, Yanyan Yang, Yan Liu, Yinfeng Zhang, Hong Xu, Mengpeng Li, Murugavel Ponnusamy, Kun Wang, Jian-Xun Wang, Pei-Feng Li
FGFR1 is a well known molecular target for anticancer therapy. Many studies have proved that the regulation of FGFR1 activity is a promising therapeutic approach to treat a series of cancers. Therefore, the development of potent inhibitors has consequently become a key focus in the present drug discovery, and it is encouraging that several highly selective FGFR1 inhibitors have been identified from various sources in recent years. Areas covered: This article reviews patents and patent applications related to selective FGFR1 inhibitors published from 2010 to 2016...
December 26, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27974186/classical-and-non-classical-causes-of-gh-deficiency-in-the-paediatric-age
#19
REVIEW
Natascia Di Iorgi, Giovanni Morana, Anna Elsa Maria Allegri, Flavia Napoli, Roberto Gastaldi, Annalisa Calcagno, Giuseppa Patti, Sandro Loche, Mohamad Maghnie
Growth hormone deficiency (GHD) may result from a failure of hypothalamic GHRH production or release, from congenital disorders of pituitary development, or from central nervous system insults including tumors, surgery, trauma, radiation or infiltration from inflammatory diseases. Idiopathic, isolated GHD is the most common sporadic form of hypopituitarism. GHD may also occur in combination with other pituitary hormone deficiencies, and is often referred to as hypopituitarism, combined pituitary hormone deficiency (CPHD), multiple pituitary hormone deficiency (MPHD) or panhypopituitarism...
December 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27974047/fgfr1-and-ntrk3-actionable-alterations-in-wild-type-gastrointestinal-stromal-tumors
#20
Eileen Shi, Juliann Chmielecki, Chih-Min Tang, Kai Wang, Michael C Heinrich, Guhyun Kang, Christopher L Corless, David Hong, Katherine E Fero, James D Murphy, Paul T Fanta, Siraj M Ali, Martina De Siena, Adam M Burgoyne, Sujana Movva, Lisa Madlensky, Gregory M Heestand, Jonathan C Trent, Razelle Kurzrock, Deborah Morosini, Jeffrey S Ross, Olivier Harismendy, Jason K Sicklick
BACKGROUND: About 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies. METHODS: We performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations...
December 14, 2016: Journal of Translational Medicine
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