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https://www.readbyqxmd.com/read/29242604/ribosomal-protein-s15a-promotes-tumor-angiogenesis-via-enhancing-wnt-%C3%AE-catenin-induced-fgf18-expression-in-hepatocellular-carcinoma
#1
Pengyi Guo, Yi Wang, Chunxiu Dai, Chonglin Tao, Fang Wu, Xiaozai Xie, Haitao Yu, Qiandong Zhu, Junjian Li, Longyun Ye, Fuxiang Yu, Yunfeng Shan, Zhengping Yu, Renumathy Dhanasekaran, Rongyuan Zheng, Gang Chen
Ribosomal protein s15a (RPS15A) plays a promotive role in the mRNA/ribosome interactions during early translation. Our previous study has found that inhibiting RPS15A expression can decrease proliferation and induce cell cycle arrest in hepatocellular carcinoma (HCC) cell lines. However, the mechanism underlying the involvement of RPS15A in HCC pathogenesis and the clinical significance of RPS15A expression remain unclear. In this study, an evaluation of RPS15A expression in 110 surgically resected HCCs and matched tumor-adjacent normal tissues revealed an overexpression of RPS15A in HCC, which was correlated with worse survival...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29242050/mutant-fgfr3-associated-with-saddan-disease-causes-cytoskeleton-disorganization-through-plc%C3%AE-1-src-mediated-paxillin-hyperphosphorylation
#2
R Montone, M G Romanelli, A Baruzzi, F Ferrarini, E Liboi, P M-J Lievens
K650M/E substitutions in the Fibroblast growth factor receptor 3 (FGFR3) are associated with Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN) and Thanatophoric Dysplasia type II (TDII), respectively. Both SADDAN and TDII present with affected endochondral ossification marked by impaired chondrocyte functions and growth plate disorganization. In vitro, K650M/E substitutions confer FGFR3 constitutive kinase activity leading to impaired biosynthesis and accumulation of immature receptors in endoplasmic reticulum (ER)/Golgi...
December 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29226855/knockdown-of-long-noncoding-rna-fgfr3-as1-induces-cell-proliferation-inhibition-apoptosis-and-motility-reduction-in-bladder-cancer
#3
Xinhui Liao, Jieqing Chen, Yuchen Liu, Anbang He, Jianting Wu, Jianli Cheng, Xintao Zhang, Zhaojie Lv, Feng Wang, Hongbing Mei
OBJECTIVES: To study the expression pattern of long non-coding RNA FGFR3 antisense transcript 1(FGFR3-AS1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing FGFR3-AS1 in bladder cancer. METHODS: The differential expression levels of FGFR3-AS1 and FGFR3 in tumor tissues and paired normal tissues were determined using Real-Time qPCR in a total of 36 patients diagnosed with bladder cancer (urothelial carcinoma). Pearson's coefficient correlation was used for expression correlation assay...
November 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29193225/biological-significance-of-tert-promoter-mutation-in-papillary-urothelial-neoplasm-of-low-malignant-potential
#4
Chung-Chieh Wang, Chao-Yuan Huang, Yu-Lin Jhuang, Chih-Chi Chen, Yung-Ming Jeng
AIMS: Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been frequently found in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 gene, and HRAS gene in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. METHODS AND RESULTS: The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs, and 34 low-grade noninvasive papillary urothelial carcinomas (NIPUCs)...
November 28, 2017: Histopathology
https://www.readbyqxmd.com/read/29170271/temporal-lobe-malformations-in-achondroplasia-expanding-the-brain-imaging-phenotype-associated-with-fgfr3-related-skeletal-dysplasias
#5
S A Manikkam, K Chetcuti, K B Howell, R Savarirayan, A M Fink, S A Mandelstam
Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the fibroblast growth factor receptor 3 (FGFR3) group of genetic skeletal disorders. Temporal lobe abnormalities have been documented in thanatophoric dysplasia and hypochondroplasia, and in 1 case of achondroplasia. We retrospectively identified 13 children with achondroplasia who underwent MR imaging of the brain between 2002 and 2015. All children demonstrated a deep transverse temporal sulcus on MR imaging. Further common neuroimaging findings were incomplete hippocampal rotation (12 children), oversulcation of the mesial temporal lobe (11 children), loss of gray-white matter differentiation of the mesial temporal lobe (5 children), and a triangular shape of the temporal horn (6 children)...
November 23, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29165379/role-of-non-coding-rnas-in-the-etiology-of-bladder-cancer
#6
REVIEW
Caterina Gulìa, Stefano Baldassarra, Fabrizio Signore, Giuliano Rigon, Valerio Pizzuti, Marco Gaffi, Vito Briganti, Alessandro Porrello, Roberto Piergentili
According to data of the International Agency for Research on Cancer and the World Health Organization (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organization Mortality), bladder is among the top ten body locations of cancer globally, with the highest incidence rates reported in Southern and Western Europe, North America, Northern Africa and Western Asia. Males (M) are more vulnerable to this disease than females (F), despite ample frequency variations in different countries, with a M:F ratio of 4...
November 22, 2017: Genes
https://www.readbyqxmd.com/read/29161613/molecular-characterization-of-urothelial-carcinoma-of-the-bladder-and-upper-urinary-tract
#7
Ji Yun Lee, Kyung Kim, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Ghee-Young Kwon, Kyoung-Mee Kim, Jeeyun Lee, Ho Yeong Lim, Se Hoon Park
PURPOSE: A better understanding of the molecular basis of urothelial carcinoma (UC) is needed to refine the clinical decision-making process. METHODS AND MATERIALS: We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC) and urinary bladder UC (UBUC) were compared...
November 18, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#8
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29122839/fgf-receptors-control-alveolar-elastogenesis
#9
Rongbo Li, John C Herriges, Lin Chen, Robert P Mecham, Xin Sun
Alveologenesis is the final step of lung development characterized by the formation of millions of alveolar septa which constitute the vast gas-exchange surface area. The genetic network driving alveologenesis is poorly understood compared to those in earlier steps of lung development. Fibroblast Growth Factor (FGF) signaling through the FGF receptors, Fgfr3 and Fgfr4 (hereafter Fgfr3;4), is critical for alveologenesis. However, the mechanisms through which they mediate this process remain unclear. Here we show that in Fgfr3;4 global mutant mice, alveolar simplification is first observed at the onset of alveologenesis at postnatal day (P) 3...
November 9, 2017: Development
https://www.readbyqxmd.com/read/29110841/heterogeneous-resistance-mechanisms-in-an-egfr-exon-19-mutated-non-small-cell-lung-cancer-patient-treated-with-erlotinib-persistent-fgfr3-mutation-localized-transformation-to-egfr-mutated-sclc-and-acquired-t790m-egfr-mutation
#10
Eric Santoni-Rugiu, Morten Grauslund, Linea C Melchior, Junia C Costa, Jens B Sørensen, Edyta M Urbanska
Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9-15 months during first-line TKI-therapy. However, type and timing of TKI-resistance cannot be predicted and several mechanisms may simultaneously/subsequently occur during TKI-treatment. In this respect, we present a 49 year-old Caucasian male ex-smoker with metastatic pulmonary adenocarcinoma (ADC) that concomitantly harbored an EGFR exon 19-mutation (p...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110262/mutational-diversity-of-lung-cancer-and-associated-lymph-nodes-an-exploratory-prospective-study-of-4-resected-ciiia-n2
#11
Antoine Legras, Hélène Roussel, Giuseppe Mangiameli, Alex Arame, Bertrand Grand, Ciprian Pricopi, Alain Badia, Laure Gibault, Cécile Badoual, Elizabeth Fabre, Pierre Laurent-Puig, Hélène Blons, Françoise Le Pimpec-Barthes
Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected...
November 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29104492/pth-1-34-ameliorates-the-osteopenia-and-delayed-healing-of-stabilized-tibia-fracture-in-mice-with-achondroplasia-resulting-from-gain-of-function-mutation-of-fgfr3
#12
Hangang Chen, Xianding Sun, Liangjun Yin, Shuai Chen, Ying Zhu, Junlan Huang, Wanling Jiang, Bo Chen, Ruobin Zhang, Lin Chen, Mao Nie, Yangli Xie, Zhongliang Deng
Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29096595/pleiotropic-actions-of-fgf23
#13
Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor α-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium-phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29080836/identification-of-a-novel-mutation-in-the-fgfr3-gene-in-a-chinese-family-with-hypochondroplasia
#14
Jing Chen, Jiangfei Yang, Suzhou Zhao, Hui Ying, Guimei Li, Chao Xu
BACKGROUND: Hypochondroplasia (HCH; OMIM 146000) is a common autosomal dominant skeletal dysplasia characterized by disproportionate short stature, short extremities, relative macrocephaly, and lumbar lordosis. Because of its clinical and genetic heterogeneity, gene mutational analysis is particularly important in diagnosis and the phenotypes may be ameliorated if diagnosed early. MATERIALS AND METHODS: In this study, we examined a Chinese family with HCH, performed an inductive analysis of their clinical features and radiographic results, and applied targeted exome sequencing (TES) technology to perform a molecular diagnosis...
October 25, 2017: Gene
https://www.readbyqxmd.com/read/29074453/exome-wide-association-study-of-pancreatic-cancer-risk
#15
Robert C Grant, Robert E Denroche, Ayelet Borgida, Carl Virtanen, Natalie Cook, Alyssa L Smith, Ashton A Connor, Julie M Wilson, Gloria Peterson, Nicholas J Roberts, Alison P Klein, Sean M Grimmond, Andrew Biankin, Sean Cleary, Malcolm Moore, Mathieu Lemire, George Zogopolous, Lincoln Stein, Steven Gallinger
We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10-6; exome-wide statistical significance threshold P<2...
October 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29068064/familial-acanthosis-nigricans-with-p-k650t-fgfr3-mutation
#16
Kensuke Fukuchi, Kazuki Tatsuno, Kayo Matsushita, Akiharu Kubo, Taisuke Ito, Yoshiki Tokura
Acanthosis nigricans (AN) is a pigmentary skin disorder, which may present in association with clinical disorders such as obesity and malignancy. Occasionally, this unique skin manifestation is seen in alliance with several skeletal disorders, such Crouzon syndrome, achondroplasia and hypochondroplasia (HCH). These orthopedic disorders are known to have genetic changes in FGFR3. Recently, AN was reported in HCH with p.K650T mutation in FGFR3, and to date, there are only three reports, comprising 18 cases, describing AN harboring this specific gene mutation...
October 25, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/29063142/molecular-therapeutic-strategies-for-fgfr3-gene-related-skeletal-dysplasia
#17
REVIEW
Jia Chen, Jiaqi Liu, Yangzhong Zhou, Sen Liu, Gang Liu, Yuzhi Zuo, Zhihong Wu, Nan Wu, Guixing Qiu
The FGFR3 gene encodes fibroblast growth factor receptor 3 protein, a negative regulator of chondrogenesis. Gain-of-function mutations result in constitutively activated FGFR3, leading to aberrant signal transduction, and accounting for inhibition of chondrocyte proliferation and differentiation. Generally, these pathogenic mutations maintain FGFR3 in an active state and cause diverse phenotypes in patients with skeletal dysplasia. For decades, studies have revealed the molecular mechanisms of constitutively activated FGFR3 and relevant therapeutic strategies...
December 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29045509/the-antibody-drug-conjugate-target-landscape-across-a-broad-range-of-tumour-types
#18
K L Moek, D J A de Groot, E G E de Vries, R S N Fehrmann
Background: Antibody-drug conjugates (ADCs), consisting of an antibody designed against a specific target at the cell membrane linked with a cytotoxic agent, are an emerging class of therapeutics. Since ADC tumour cell targets do not have to be drivers of tumour growth, ADCs are potentially relevant for a wide range of tumours currently lacking clear oncogenic drivers. Therefore, we aimed to define the landscape of ADC targets in a broad range of tumours. Materials and methods: PubMed and ClinicalTrials...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29040969/comparison-of-igh-profile-signals-using-t-4-14-and-igh-break-apart-probes-by-fish-in-multiple-myeloma
#19
Thomas Smol, Agnès Daudignon
We compared immunoglobulin heavy chain gene (IGH) signal patterns in multiple myeloma (MM) using the FGFR3-IGH and the IGH break-apart probes to facilitate their understanding and analysis. Forty-nine patients with MM were studied. FISH was performed on samples sorted with an FGFR3-IGH dual-color, dual-fusion translocation probe and an IGH dual-color break-apart rearrangement probe. The IGH deletions were found in 7 MM analyzed with the FGFR3-IGH probe and all confirmed by the IGH break-apart probe. The additional IGH signals were associated with different patterns using the IGH break-apart probe: a normal pattern in 9 cases, trisomy 14 in 3 cases, and splits of IGH in 7 cases...
October 18, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29040558/constitutively-active-fgfr3-disrupts-primary-cilium-length-and-ift20-trafficking-in-various-chondrocyte-models-of-achondroplasia
#20
Ludovic Martin, Nabil Kaci, Valentin Estibals, Nicolas Goudin, Meriem Garfa-Traore, Catherine Benoist-Lasselin, Emilie Dambroise, Laurence Legeai-Mallet
FGFR3 (fibroblast growth factor receptor 3) gain-of-function mutations cause dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The constitutive activation of FGFR3 disrupts the normal process of skeletal growth. Bone-growth anomalies have been identified in skeletal ciliopathies, in which primary cilia (PC) function is disrupted. In human ACH and TD, the impact of FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the constitutively-active FGFR3 perturbed PC length and the sorting and trafficking of IFT20 to the PC...
October 4, 2017: Human Molecular Genetics
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