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https://www.readbyqxmd.com/read/29656749/tumor-associated-macrophages-support-the-growth-of-fgf9-induced-lung-adenocarcinoma-by-multiple-mechanisms
#1
Ahmed E Hegab, Mari Ozaki, Shizuko Kagawa, Junko Hamamoto, Hiroyuki Yasuda, Katsuhiko Naoki, Kenzo Soejima, Yongjun Yin, Tomonari Kinoshita, Tomonori Yaguchi, Yutaka Kawakami, David M Ornitz, Tomoko Betsuyaku
OBJECTIVES: Tumor-associated macrophages (TAMs) are known to promote tumorigenesis but the mechanism(s) remain elusive. We have developed a mouse model of lung cancer that is initiated through an inducible overexpression of fibroblast growth factor 9 (FGF9) in type-2 pneumocytes. Expression of FGF9 in adult lungs resulted in a rapid development of multiple adenocarcinoma-like tumor nodules, and is associated with an intense immunological reaction. The purpose of this study is to characterize the immune response to the FGF9-induced lung adenocarcinoma and to determine the contribution of TAMs to growth and survival of these tumors...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29656442/treatment-emergent-hypertension-and-efficacy-in-the-phase-3-study-of-e7080-lenvatinib-in-differentiated-cancer-of-the-thyroid-select
#2
Lori J Wirth, Makoto Tahara, Bruce Robinson, Sanjeev Francis, Marcia S Brose, Mouhammed Amir Habra, Kate Newbold, Naomi Kiyota, Corina E Dutcus, Elton Mathias, Matthew Guo, Steven I Sherman, Martin Schlumberger
BACKGROUND: Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT)...
April 14, 2018: Cancer
https://www.readbyqxmd.com/read/29653011/-advance-in-clinical-research-on-antley-bixler-syndrome
#3
Min Xie, Hongying Wang, Linqi Chen, Haibo Li, Hong Li
Antley-Bixler syndrome (ABS) is a rare childhood disorder affecting skeletal development. Some patients may also have genital anomalies and impaired steroidogenesis. Diagnostic criteria for ABS has not been fully established, though craniosynostosis, midface hypoplasia and elbow synostosis are minimum requirements. The etiology of ABS is complex, which included autosomal dominant form caused by FGFR2 gene mutations, autosomal recessive form caused by POR gene mutations, and high oral dose of fluconazole during pregnancy...
April 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29588807/placental-surface-area-mediates-the-association-between-fgfr2-methylation-in-placenta-and-full-term-low-birth-weight-in-girls
#4
Fu-Ying Tian, Xi-Meng Wang, Chuanbo Xie, Bo Zhao, Zhongzheng Niu, Lijun Fan, Marie-France Hivert, Wei-Qing Chen
Background: Fibroblast growth factor receptor 2 ( FGFR2 ) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29576506/overexpressing-dominant-negative-fgfr2-iiib-impedes-lung-branching-morphogenesis-in-pigs
#5
Qin Chen, Bin Fang, Ying Wang, Chu Li, Xiaoxue Li, Ronggen Wang, Qiang Xiong, Lining Zhang, Yong Jin, Manling Zhang, Xiaorui Liu, Lin Li, Lisha Mou, Rongfeng Li, Haiyuan Yang, Yifan Dai
Genetic studies with mouse models have shown that fibroblast growth factor receptor 2-IIIb (FGFR2-IIIb) plays crucial roles in lung development and differentiation. To evaluate the effect of FGFR2-IIIb in pig lung development, we employed somatic cell nuclear transfer (SCNT) technology to generate transgenic pig fetuses overexpressing the transmembrane (dnFGFR2-IIIb-Tm) and soluble (dnFGFR2-IIIb-HFc) forms of the dominant-negative human FGFR2-IIIb driven by the human surfactant protein C (SP-C) promoter, which was specifically expressed in lung epithelia...
February 14, 2018: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/29573334/fgfr2-amplification-is-predictive-of-sensitivity-to-regorafenib-in-gastric-and-colorectal-cancers-in-vitro
#6
Yongjun Cha, Hwang-Phill Kim, Yoojoo Lim, Sae-Won Han, Sang-Hyun Song, Tae-You Kim
Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker has been identified for predicting sensitivity to regorafenib. Here, we investigated preclinical activity of regorafenib in gastric and colorectal cancer cells to identify genetic alterations associated with sensitivity to regorafenib. Mutation profiles and copy number assays of regorafenib target molecules indicated that amplification of FGFR2 was the only genetic alteration associated with in vitro sensitivity to regorafenib...
March 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29573058/molecular-genomic-landscapes-of-hepatobiliary-cancer
#7
REVIEW
Tatsuhiro Shibata, Yasuhito Arai, Yasushi Totoki
Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) are more frequent in East Asia including Japan. Compiling 1,340 multi-ethnic HCC genomes, the largest cohort ever reported, identified comprehensive landscape of HCC driver genes, which constitutes three core drivers (TP53, TERT and WNT signaling) and combination of infrequent alterations in various cancer pathways. By contrast, five core driver genes (TP53, ARID1A, KRAS, SMAD4 and BAP1) with characteristic molecular alterations including fusion transcripts involving FGFR2 and the PKA pathway, and IDH1/2 mutation constituted the BTC genomes...
March 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29572226/a-large-scale-exome-wide-association-study-of-han-chinese-women-identifies-three-novel-loci-predisposing-to-breast-cancer
#8
Bo Zhang, Men-Yun Chen, Yu-Jun Sheng, Xian-Bo Zhuo, Ping Gao, Fu-Sheng Zhou, Bo Liang, Jun Zu, Qin Zhang, Sufyan Suleman, Yi-Hui Xu, Min-Gui Xu, Jin-Kai Xu, Chen-Cheng Liu, Nikolaos Giannareas, Ji-Han Xia, Yuan Zhao, Zhong-Lian Huang, Zhen Yang, Huaidong Cheng, Na Li, Yan-Yan Hong, Wei Li, Min-Jun Zhang, Ke-Da Yu, Guoliang Li, Meng-Hong Sun, Zhen-Dong Chen, Gong-Hong Wei, Zhi-Ming Shao
Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g. ESR1, FGFR2 and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4...
March 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29561715/genetic-analysis-of-syndromic-and-nonsyndromic-patients-with-craniosynostosis-identifies-novel-mutations-in-the-twist1-and-efnb1-genes
#9
Despina Apostolopoulou, Olga S Kaxira, Angeliki Hatzaki, Kanaris P Panagopoulos, Konstantinos Alexandrou, Alexander Stratoudakis, Panagoula Kollia, Vassiliki Aleporou
INTRODUCTION: Craniosynostosis, the premature fusion of cranial sutures, is usually divided into 2 major categories: syndromic and nonsyndromic. Mutations in the FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1 genes cause the common craniosynostosis syndromes Muenke, Crouzon and Crouzon with acanthosis nigricans, Apert, Pfeiffer, Saethre-Chotzen, and Craniofrontonasal. Overlapping features among craniosynostosis syndromes, phenotypic heterogeneity even within the same syndrome, especially in the case of Muenke syndrome, and inadequate clinical evaluation can lead to misdiagnosis, which molecular testing can help clarify...
January 1, 2018: Cleft Palate-craniofacial Journal
https://www.readbyqxmd.com/read/29557836/glaucoma-with-crouzon-syndrome
#10
Abdulaziz Anazi Alshamrani, Sami Al-Shahwan
BACKGROUND: Crouzon syndrome is the most common form of craniosynostosis, and mutations in the fibroblast growth factor receptor 2 and 3 (FGFR2 and FGFR3) genes are implicated in its pathogenesis. OBSERVATION: A 10-year-old female patient with Crouzon syndrome and congenital glaucoma treated with trabeculectomy and ocular hypotensive medications was examined. The patient had proptosis, exposure keratopathy, megalocornea, thin central corneal thickness, a shallow anterior chamber, mild anterior subcapsular cataract, and a cup-to-disc ratio of 0...
March 19, 2018: Journal of Glaucoma
https://www.readbyqxmd.com/read/29550217/demographic-characteristics-of-craniosynostosis-patients-in-asia
#11
Il Hwan Byun, Jong Won Hong, Mohammed Ahmed Hussein, Yong Oock Kim
PURPOSE: Craniosynostosis (CRS) is a congenital condition resulting premature fusion of one or more cranial sutures. CRS is classified according to the involved sutures into sagittal, metopic, unicoronal, unilambdoid, bicoronal, and multiple-suture CRS, with sagittal suture fusion known to be the most common type. Although multiple studies have presented demographic characteristics of CRS patients, to date, there is no study representing an Asian population. We sought to compare the demographic characteristics of Asian patients to those of Western patients, considering previous reports...
February 21, 2018: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29546640/molecular-defects-in-braf-wild-type-ameloblastomas-and-craniopharyngiomas-differences-in-mutation-profiles-in-epithelial-derived-oropharyngeal-neoplasms
#12
Stephan Bartels, Akinyele Adisa, Timothy Aladelusi, Juliana Lemound, Angelika Stucki-Koch, Sami Hussein, Hans Kreipe, Christian Hartmann, Ulrich Lehmann, Kais Hussein
The aim of this study was to evaluate the mutation profile of BRAF wild-type craniopharyngiomas and ameloblastomas. Pre-screening by immunohistochemistry and pyrosequencing for identifying BRAF wild-type tumors was performed on archived specimens of ameloblastic tumors (n = 20) and craniopharyngiomas (n = 62). Subsequently, 19 BRAF wild-type tumors (nine ameloblastic tumors and ten craniopharyngiomas) were analyzed further using next-generation sequencing (NGS) targeting hot spot mutations of 22 cancer-related genes...
March 15, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29535768/neuropilin-1-mediates-keratinocyte-growth-factor-signaling-in-adipose-derived-stem-cells-potential-involvement-in-adipogenesis
#13
Simona Ceccarelli, Cristina Nodale, Enrica Vescarelli, Paola Pontecorvi, Valeria Manganelli, Giovanni Casella, Maria Giuseppina Onesti, Maurizio Sorice, Ferdinando Romano, Antonio Angeloni, Cinzia Marchese
Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29526646/inactivation-of-fgfr2-gene-in-mouse-secondary-palate-mesenchymal-cells-leads-to-cleft-palate
#14
Jiu-Zhen Jin, Zhenmin Lei, Zi-Jian Lan, Partha Mukhopadhyay, Jixiang Ding
Numerous studies have been conducted to understand the molecular mechanisms controlling mammalian secondary palate development such as growth, reorientation and fusion. However, little is known about the signaling factors regulating palate initiation. Mouse fibroblast growth factor (FGF) receptor 2 gene (Fgfr2) is expressed on E11.5 in the palate outgrowth within the maxillary process, in a region that is responsible for palate cell specification and shelf initiation. Fgfr2 continues to express in palate on E12...
March 8, 2018: Reproductive Toxicology
https://www.readbyqxmd.com/read/29514108/low-level-clonal-fgfr2-amplification-defines-a-unique-molecular-subtype-of-intrahepatic-cholangiocarcinoma-in-a-chinese-population
#15
Xiao-Hong Pu, Qing Ye, Jun Yang, Hong-Yan Wu, Xi-Wei Ding, Jiong Shi, Liang Mao, Xiang-Shan Fan, Jun Chen, Yu-Dong Qiu, Qin Huang
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer rarely curable by surgery that is increasing rapidly in incidence. Chromosomal translocations and amplifications of the fibroblast growth factor receptor 2 (FGFR2) locus are present in several kinds of tumors including ICC, but their incidence has not been assessed in Chinese patients. Using break-apart probes and by determining the ratios of FGFR2/chromosome enumeration probe (CEP) 10 double-color probes, we evaluated 122 ICCs for the presence of FGFR2 translocations and amplifications, respectively, by fluorescence in situ hybridization (FISH)...
March 4, 2018: Human Pathology
https://www.readbyqxmd.com/read/29487166/dynamic-changes-in-sox2-spatio-temporal-expression-promote-the-second-cell-fate-decision-through-fgf4-fgfr2-signalling-in-preimplantation-mouse-embryos
#16
Tapan Kumar Mistri, Wibowo Arindrarto, Wei Ping Ng, Choayang Wang, Leng Hiong Lim, Lili Sun, Ian Chambers, Thorsten Wohland, Paul Robson
Oct4 and Sox2 regulate the expression of target genes such as Nanog, Fgf4 and Utf1 , by binding to their respective regulatory motifs. Their functional cooperation is reflected in their ability to heterodimerise on adjacent cis regulatory motifs, the composite Sox/Oct motif. Given that Oct4 and Sox2 regulate many developmental genes, a quantitative analysis of their synergistic action on different Sox/Oct motifs would yield valuable insights into the mechanisms of early embryonic development. In this study, we measured binding affinities of Oct4 and Sox2 to different Sox/Oct motifs using fluorescence correlation spectroscopy (FCS)...
February 27, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29483804/two-patients-with-apert-syndrome-with-different-mutations-the-importance-of-early-diagnosis
#17
Esra Işık, Tahir Atik, Hüseyin Onay, Ferda Özkınay
Apert syndrome is an autosomal dominant craniosynostosis syndrome accompanied by limb anomalies. The fibroblast growth factor receptor 2 ( FGFR2 ) gene is responsible for the disease and two different heterozygous mutations, p.Pro253Arg and p.Ser252Trp, have been defined as responsible in the majority of cases of Apert syndrome. In this case report, two patients with Apert syndrome with two different FGFR2 gene mutations are presented. Case-1, a 4-month-old boy with craniosynostosis and syndactyly was referred to pediatric genetic clinic...
December 2017: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/29476210/a-child-with-apert-syndrome-and-sturge-weber-syndrome-could-fibronectin-or-the-ras-mapk-signaling-pathway-be-the-connection
#18
Ai Peng Tan, Wui Khean Chong
BACKGROUND: Apert syndrome is one of the most common craniosynostosis syndrome caused by mutation in genes encoding fibroblast growth factor receptor 2 (FGFR2). Craniosynostosis, midfacial hypoplasia, and syndactyly/symphalangism are features of this syndrome. Sturge-Weber syndrome (SWS) on the other hand is a congenital neurocutaneous disorder characterized by facial port-wine stains (PWSs) and leptomeningeal vascular capillary malformations. In 2013, the causative mutation underlying SWS (p...
February 23, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29460642/novel-targeted-therapy-strategies-for-biliary-tract-cancers-and-hepatocellular-carcinoma
#19
Thomas T DeLeon, Daniel H Ahn, James M Bogenberger, Panos Z Anastasiadis, Mansi Arora, Ramesh K Ramanathan, Bashar A Aqel, George Vasmatzis, Mark J Truty, Rahmi Oklu, Tanios S Bekaii-Saab, Mitesh J Borad
Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement...
February 20, 2018: Future Oncology
https://www.readbyqxmd.com/read/29458881/prenatal-diagnosis-of-short-rib-polydactyly-syndrome-type-iii-or-short-rib-thoracic-dysplasia-3-with-or-without-polydactyly-srtd3-associated-with-compound-heterozygous-mutations-in-dync2h1-in-a-fetus
#20
Chih-Ping Chen, Tsang-Ming Ko, Tung-Yao Chang, Schu-Rern Chern, Shin-Wen Chen, Shih-Ting Lai, Tzu-Yun Chuang, Wayseen Wang
OBJECTIVE: We present the perinatal imaging findings and molecular genetic analysis in a fetus with short-rib polydactyly syndrome (SRPS) type III or short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3). CASE REPORT: A 29-year-old, primigravid woman was referred for genetic counseling at 15 weeks of gestation because of abnormal ultrasound findings of short limbs, a narrow chest and bilateral polydactyly of the hands and feet, consistent with a diagnosis of SRPS type III...
February 2018: Taiwanese Journal of Obstetrics & Gynecology
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