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https://www.readbyqxmd.com/read/28223168/prognostic-alternative-mrna-splicing-signature-in-non-small-cell-lung-cancer
#1
Yuan Li, Nan Sun, Zhiliang Lu, Shouguo Sun, Jianbing Huang, Zhaoli Chen, Jie He
Alternative splicing provides a major mechanism to generate protein diversity. Increasing evidence suggests a link of dysregulation of splicing associated with cancer. Genome-wide alternative splicing profiling in lung cancer remains largely unstudied. We generated alternative splicing profiles in 491 lung adenocarcinoma (LUAD) and 471 lung squamous cell carcinoma (LUSC) patients in TCGA using RNA-seq data, prognostic models and splicing networks were built by integrated bioinformatics analysis. A total of 3,691 and 2,403 alternative splicing events were significantly associated with patient survival in LUAD and LUSC, respectively, including EGFR, CD44, PIK3C3, RRAS2, MAPKAP1 and FGFR2...
February 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28205043/a-polygenic-risk-score-for-breast-cancer-risk-in-a-taiwanese-population
#2
Yi-Chen Hsieh, Shih-Hsin Tu, Chien-Tien Su, Er-Chieh Cho, Chih-Hsiung Wu, Mao-Chih Hsieh, Shiyng-Yu Lin, Yun-Ru Liu, Chin-Sheng Hung, Hung-Yi Chiou
BACKGROUND: Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population. METHODS: In total, 446 breast cancer patients and 514 healthy controls were recruited for this case-control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC)...
February 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28193689/signaling-by-fgf-receptor-2-not-fgf-receptor-1-regulates-myelin-thickness-through-activation-of-erk1-2-mapk-which-promotes-mtorc1-activity-in-an-akt-independent-manner
#3
M Furusho, A Ishii, R Bansal
FGF signaling has emerged as a significant 'late-stage' regulator of myelin thickness in the CNS, independent of oligodendrocyte differentiation. Therefore, it is critically important to identify the specific FGF-Receptor-type and its downstream signaling molecules in oligodendrocytes to obtain better insights into the regulatory mechanisms of myelin growth. Here, we show that FGF-Receptor-type-2 (FGFR2) is highly enriched at the paranodal loops of myelin. Conditional ablation of this receptor-type, but not FGF-Receptor-type-1 (FGFR1), resulted in attenuation of myelin growth, expression of major myelin genes, key transcription factor Myrf and ERK1/2 activity...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28178648/polymorphisms-of-esr1-ugt1a1-hcn1-map3k1-and-cyp2b6-are-associated-with-the-prognosis-of-hormone-receptor-positive-early-breast-cancer
#4
Sung-Hsin Kuo, Shi-Yi Yang, San-Lin You, Huang-Chun Lien, Ching-Hung Lin, Po-Han Lin, Chiun-Sheng Huang
In this study, we investigated whether single nucleotide polymorphisms (SNPs) identified by genome-wide association study (GWAS) (MAP3K1, FGFR2, TNRC9, HCN1, and 5p12), and SNPs involved in the metabolism of estrogen (CYP19, COMT, ESR1, and UGT1A1), tamoxifen (CYP2C9, CYP2C19, CYP3A5, and CYP2D6), and chemotherapeutic agents (ABCB1, ALDH3A1, and CYP2B6) are associated with the prognoses of 414 hormone receptor (HR)-positive early breast cancers with negative or 1 to 3 nodal metastases. At a median follow-up period of 10...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28151998/effects-of-fgfr2-kinase-activation-loop-dynamics-on-catalytic-activity
#5
Jerome M Karp, Samuel Sparks, David Cowburn
The structural mechanisms by which receptor tyrosine kinases (RTKs) regulate catalytic activity are diverse and often based on subtle changes in conformational dynamics. The regulatory mechanism of one such RTK, fibroblast growth factor receptor 2 (FGFR2) kinase, is still unknown, as the numerous crystal structures of the unphosphorylated and phosphorylated forms of the kinase domains show no apparent structural change that could explain how phosphorylation could enable catalytic activity. In this study, we use several enhanced sampling molecular dynamics (MD) methods to elucidate the structural changes to the kinase's activation loop that occur upon phosphorylation...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28141641/long-term-evaluation-of-mandibular-growth-in-children-with-fgfr2-mutations
#6
John C Kolar, Kanlaya Ditthakasem, Jeffrey A Fearon
BACKGROUND: Understanding mandibular growth in children with fibroblast growth factor receptor 2 (FGFR2) mutations is important for planning the degree of midface advancement, and for determining the best treatment for obstructive sleep apnea. Yet, relatively little is known about growth of the unoperated mandible in affected children. The purpose of this study was to evaluate mandibular growth through skeletal maturity in Apert, Crouzon, and Pfeiffer syndromes. METHODS: A retrospective chart review was performed...
January 30, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28132898/investigation-of-g-quadruplex-formation-in-the-fgfr2-promoter-region-and-its-transcriptional-regulation-by-liensinine
#7
Lulu Zhang, Wei Tan, Jiang Zhou, Ming Xu, Gu Yuan
BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in breast cancer tissues and cells, and has been shown to be a susceptibility factor for breast cancer. In this study, we found that the G-rich sequences in the FGFR2 promoter region can form G-quadruplexes, which could be the target and inhibitor of the FGFR2 gene. METHODS: Initially, the formation of G-quadruplexes was confirmed by ESI-MS and CD, and DMS footprinting experiments gave the folding pattern of the G-quadruplexes...
January 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28129744/vitiligo-blood-transcriptomics-provides-new-insights-into-disease-mechanisms-and-identifies-potential-novel-therapeutic-targets
#8
Rama Dey-Rao, Animesh A Sinha
BACKGROUND: Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. METHODS: We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile...
January 28, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28127173/crouzon-s-syndrome-a-rare-genetic-disorder
#9
Anupriya Kaushik, Hindpal Bhatia, Naresh Sharma
: Crouzon's syndrome, also known as brachial arch syndrome, is an autosomal dominant disorder with complete penetrance and variable expressivity. Described by a French neurosurgeon in 1912, it is a rare genetic disorder. Crouzon's syndrome is caused by mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. Normally, the sutures in the human skull fuse after the complete growth of the brain, but if any of these sutures close early, then it may interfere with the growth of the brain...
October 2016: International Journal of Clinical Pediatric Dentistry
https://www.readbyqxmd.com/read/28123544/molecular-heterogeneity-in-the-novel-fusion-gene-apip-fgfr2-diversity-of-genomic-breakpoints-in-gastric-cancer-with-high-level-amplifications-at-11p13-and-10q26
#10
Takashi Okuda, Tomohiko Taki, Kazuhiro Nishida, Yoshiaki Chinen, Hisao Nagoshi, Chouhei Sakakura, Masafumi Taniwaki
Several novel fusion transcripts were identified by next-generation sequencing in gastric cancer; however, the breakpoint junctions have yet to be characterized. The present study characterized a plethora of APIP-FGFR2 genomic breakpoints in the SNU-16 gastric cancer cell line, which harbored homogeneously staining regions (hsrs) and double minute chromosomes. Oligonucleotide microarrays revealed high-level amplifications at chromosomes 8q24.1 (0.8 Mb region), 10q26 (1.1 Mb) and 11p13 (1.1 Mb). These amplicons contained MYC and PVT1 at chromosome 8q24...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28123344/deformed-skull-morphology-is-caused-by-the-combined-effects-of-the-maldevelopment-of-calvarias-cranial-base-and-brain-in-fgfr2-p253r-mice-mimicking-human-apert-syndrome
#11
Fengtao Luo, Yangli Xie, Wei Xu, Junlan Huang, Siru Zhou, Zuqiang Wang, Xiaoqing Luo, Mi Liu, Lin Chen, Xiaolan Du
Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2(+/P253R-Neo) mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28122360/acquired-resistance-to-ly2874455-in-fgfr2-amplified-gastric-cancer-through-an-emergence-of-novel-fgfr2-acsl5-fusion
#12
Sun Young Kim, Taejin Ahn, Heejin Bang, Jun Soo Ham, Jusun Kim, Seung Tae Kim, Jiryeon Jang, Moonhee Shim, So Young Kang, Se Hoon Park, Byung Hoon Min, Hyuk Lee, Won Ki Kang, Kyoung-Mee Kim, Woongyang Park, Jeeyun Lee
BACKGROUND: Fibroblast growth factor 2 (FGFR2) amplification, occurring in ~2-9% of gastric cancers (GC), is associated with poor overall survival. RESULTS: RNA sequencing identified a novel FGFR2-ACSL5 fusion in the resistant tumor that was absent from the matched pre-treatment tumor. The FGFR2-amplified PDC line was sensitive to FGFR inhibitors whereas the PDC line with concomitant FGFR2 amplification and FGFR2-ACSL5 fusion exhibited resistance. Additionally, the FGFR2-amplified GC PDC line, which was initially sensitive to FGFR2 inhibitors, subsequently also developed resistance...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28121883/evaluating-the-efficacy-of-monobloc-distraction-in-the-crouzon-pfeiffer-craniofacial-deformity-using-geometric-morphometrics
#13
Richard Visser, Clifford F Ruff, Freida Angullia, Allan J T Ponniah, N U Owase Jeelani, Jonathan A Britto, Maarten J Koudstaal, David J Dunaway
BACKGROUND: Crouzon-Pfeiffer syndrome is caused by mutations predominantly in the FGFR2 gene leading to syndromic craniosynostosis and midfacial hypoplasia. Monobloc distraction aims to correct both functional and aesthetic disharmony as a result of midfacial hypoplasia. This study evaluates the corrective effects and effectiveness of monobloc distraction in Crouzon-Pfeiffer patients. METHODS: Preoperative and postoperative scans were collected from 20 Crouzon and two Pfeiffer patients aged 7 to 20 years...
February 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28119489/pi3k-inhibitors-synergize-with-fgfr-inhibitors-to-enhance-antitumor-responses-in-fgfr2-mutant-endometrial-cancers
#14
Leisl Packer, Xinyan Geng, Vanessa F Bonazzi, Robert Ju, Clare Mahon, Margaret C Cummings, Sally-Anne Stephenson, Pamela M Pollock
Improved therapeutic approaches are needed for the treatment of recurrent and metastatic endometrial cancer (EC). ECs display hyper-activation of the MAPK and PI3K pathways, the result of somatic aberrations in genes such as FGFR2, KRAS, PTEN, PIK3CA and PIK3R1. FGFR2, as well as the PI3K pathway, have emerged as potential therapeutic targets in EC. Activation of the PI3K pathway is seen in >90% of FGFR2mutant ECs. This study aimed to examine the efficacy of the pan-FGFR inhibitor BGJ398 with pan-PI3K inhibitors (GDC-0941, BKM120) and the p110α-selective inhibitor BYL719...
January 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28118661/trinucleotide-repeat-expansion-in-the-transcription-factor-4-tcf4-gene-leads-to-widespread-mrna-splicing-changes-in-fuchs-endothelial-corneal-dystrophy
#15
Eric D Wieben, Ross A Aleff, Xiaojia Tang, Malinda L Butz, Krishna R Kalari, Edward W Highsmith, Jin Jen, George Vasmatzis, Sanjay V Patel, Leo J Maguire, Keith H Baratz, Michael P Fautsch
Purpose: To identify RNA missplicing events in human corneal endothelial tissue isolated from Fuchs' endothelial corneal dystrophy (FECD). Methods: Total RNA was isolated and sequenced from corneal endothelial tissue obtained during keratoplasty from 12 patients with FECD and 4 patients undergoing keratoplasty or enucleation for other indications. The length of the trinucleotide repeat (TNR) CTG in the transcription factor 4 (TCF4) gene was determined using leukocyte-derived DNA analyzed by a combination of Southern blotting and Genescan analysis...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28116419/-expression-and-localization-of-fgfr-family-in-squamous-cell-carcinoma-of-head-and-neck
#16
Chao-Ji Shi, Rong Zhou, Yong Han, Wen-Jie Tao, Shu-Yang Sun, Zhi-Yuan Zhang
PURPOSE: To investigate the expression and localization of FGFR family in squamous cell carcinoma of head and neck (SCCHN) cell lines. METHODS: Total protein was extracted from 10 SCCHN cell lines and the expression of FGFR was detected by Western blot. The localization of FGFR was further demonstrated by immunofluorescence staining in SCC25 and HN4 cell lines. Gray value was measured by Image J. GraphPad Prism 5.01 software package was used for data processing and analysis...
October 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28102887/clinical-trial-of-nintedanib-in-patients-with-recurrent-or-metastatic-salivary-gland-cancer-of-the-head-and-neck-a-multicenter-phase-2-study-korean-cancer-study-group-hn14-01
#17
Youjin Kim, Su Jin Lee, Ji Yun Lee, Se-Hoon Lee, Jong-Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha-Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß)...
January 19, 2017: Cancer
https://www.readbyqxmd.com/read/28098224/association-of-genome-wide-association-study-gwas-identified-snps-and-risk-of-breast-cancer-in-an-indian-population
#18
Rajini Nagrani, Sharayu Mhatre, Preetha Rajaraman, Nilanjan Chatterjee, Mohammad R Akbari, Paolo Boffetta, Paul Brennan, Rajendra Badwe, Sudeep Gupta, Rajesh Dikshit
To date, no studies have investigated the association of the GWAS-identified SNPs with BC risk in Indian population. We investigated the association of 30 previously reported and replicated BC susceptibility SNPs in 1,204 cases and 1,212 controls from a hospital based case-control study conducted at the Tata Memorial Hospital, Mumbai. As a measure of total susceptibility burden, the polygenic risk score (PRS) for each individual was defined by the weighted sum of genotypes from 21 independent SNPs with weights derived from previously published estimates of association odds-ratios...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093295/in-silico-enhancement-of-the-stability-and-activity-of-keratinocyte-growth-factor
#19
Mansour Poorebrahim, Solmaz Sadeghi, Raziyeh Ghorbani, Matin Asghari, Mohammad Foad Abazari, Hourieh Kalhor, Hamzeh Rahimi
Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family, has been implicated in some biological processes such as cell proliferation, development and differentiation. High mitogenic activity of this protein has made it very suitable for repairing radiation-and chemotherapy-induced damages. Palifermin, which has been developed from human KGF, is clinically applied to reduce the incidence and duration of cancer therapeutic agents. However, the activity of Palifermin is limited during treatment due to its poor stability...
January 16, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28088441/resveratrol-limits-epithelial-to-mesenchymal-transition-through-modulation-of-khsrp-hnrnpa1-dependent-alternative-splicing-in-mammary-gland-cells
#20
Arfa Moshiri, Margherita Puppo, Martina Rossi, Roberto Gherzi, Paola Briata
Resveratrol (RESV) is a natural polyphenolic compound endowed with anti-inflammatory, anti-proliferative, as well as pro-apoptotic activities that make it a potential anti-tumor compound. Here we show that RESV counteracts the TGF-β-induced Epithelial to Mesenchymal Transition (EMT) phenotype in mammary gland cells and affects the alternative exon usage of pre-mRNAs that encode crucial factors in adhesion and migration -including CD44, ENAH, and FGFR2- in a panel of immortalized and transformed mammary gland cells...
January 11, 2017: Biochimica et Biophysica Acta
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