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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
#1
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
#2
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
#3
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. KGF, which has been developed from human KGF, is clinically applied to reduce the incidence and duration of cancer therapeutic agents. However, the activity of KGF is limited during treatment due to its poor stability...
January 13, 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
#4
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
https://www.readbyqxmd.com/read/28069589/analysis-of-the-fgfr2c342y-mouse-model-shows-condensation-defects-due-to-misregulation-of-sox9-expression-in-prechondrocytic-mesenchyme
#5
Emma Peskett, Samin Kumar, William Baird, Janhvi Jaiswal, Ming Li, Priyanca Patel, Jonathan A Britto, Erwin Pauws
Syndromic craniosynostosis caused by mutations in FGFR2 is characterised by developmental pathology in both endochondral and membranous skeletogenesis. Detailed phenotypic characterisation of features in the membranous calvarium, the endochondral cranial base and other structures in the axial and appendicular skeleton has not been performed at embryonic stages. We investigated bone development in the Crouzon mouse model (Fgfr2(C342Y)) at pre- and post-ossification stages to improve understanding of the underlying pathogenesis...
January 9, 2017: Biology Open
https://www.readbyqxmd.com/read/28060197/identical-twins-discordant-for-metopic-craniosynostosis-evidence-of-epigenetic-influences
#6
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
#7
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/28052872/fgfr2-is-integral-for-bladder-mesenchyme-patterning-and-function
#8
Youko Ikeda, Irina Zabbarova, Caitlin M Schaefer, Daniel S Bushnell, William C de Groat, Anthony J Kanai, Carlton M Bates
BACKGROUND: While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown fibroblast growth factor receptor 2 (Fgfr2) is necessary for kidney and ureter mesenchymal development. OBJECTIVE: Out objective was to determine the role of Fgfr2 in bladder mesenchyme. METHODS: We used Tbx18cre mice to delete Fgfr2 in bladder mesenchyme (Fgfr2BM-/-)...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28043904/liver-cancer-cell-of-origin-molecular-class-and-effects-on-patient-prognosis
#9
REVIEW
Daniela Sia, Augusto Villanueva, Scott L Friedman, Josep M Llovet
Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis, and clarify the classes of liver cancer, based on molecular features and how these affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC vs iCCA are distinct, although they have overlapping risk factors and pathways of oncogenesis...
December 30, 2016: Gastroenterology
https://www.readbyqxmd.com/read/28041631/targeting-fibroblast-growth-factor-pathways-in-endometrial-cancer
#10
Boris Winterhoff, Gottfried E Konecny
Novel treatments that improve outcomes for patients with recurrent or metastatic endometrial cancer (EC) remain an unmet need. Aberrant signaling by fibroblast growth factors (FGFs) and FGF receptors (FGFRs) has been implicated in several human cancers. Activating mutations in FGFR2 have been found in up to 16% of ECs, suggesting an opportunity for targeted therapy. This review summarizes the role of the FGF pathway in angiogenesis and EC, and provides an overview of FGFR-targeted therapies under clinical development for the treatment of EC...
November 11, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28034880/polyclonal-secondary-fgfr2-mutations-drive-acquired-resistance-to-fgfr-inhibition-in-patients-with-fgfr2-fusion-positive-cholangiocarcinoma
#11
Lipika Goyal, Supriya K Saha, Leah Y Liu, Giulia Siravegna, Ignaty Leshchiner, Leanne G Ahronian, Jochen K Lennerz, Phuong Vu, Vikram Deshpande, Avinash Kambadakone, Benedetta Mussolin, Stephanie Reyes, Laura Henderson, Jiaoyuan Elisabeth Sun, Emily E Van Seventer, Joseph M Gurski, Sabrina Baltschukat, Barbara Schacher-Engstler, Louise Barys, Christelle Stamm, Pascal Furet, David P Ryan, James R Stone, A John Iafrate, Gad Getz, Diana Graus Porta, Ralph Tiedt, Alberto Bardelli, Dejan Juric, Ryan B Corcoran, Nabeel Bardeesy, Andrew X Zhu
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases...
December 29, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28031172/prorenin-receptor-controls-renal-branching-morphogenesis-via-wnt-%C3%AE-catenin-signaling
#12
Renfang Song, Adam Janssen, Yuwen Li, Samir S El-Dahr, Ihor V Yosypiv
The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H+-ATPase. Renal branching morphogenesis, defined as growth and branching of the ureteric bud (UB), is essential for mammalian kidney development. Previously, we demonstrated that conditional ablation of the PRR in the UB in PRRUB-/- mice causes severe defects in UB branching, resulting in marked kidney hypoplasia at birth. Here, we investigated UB transcriptome using whole-genome-based analysis of gene expression in UB cells FACS-isolated from PRRUB-/- and control kidneys at birth (P0) to determine the primary role of the PRR in terminal differentiation and growth of UB-derived collecting ducts...
December 28, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28002800/sprouty2-correlates-with-favorable-prognosis-of-gastric-adenocarcinoma-via-suppressing-fgfr2-induced-erk-phosphorylation-and-cancer-progression
#13
Yunfei Xu, Xiaoqing Yang, Zhen Li, Shuo Li, Sen Guo, Sayed Ismail, Hongda Liu, Zhihong Huang, Qing Sun, Zongli Zhang, Yuxin Chen
Fibroblast growth factor receptor 2 (FGFR2) has been identified as a predictive biomarker for unfavorable prognosis of gastric adenocarcinoma. As a well-defined antagonist in FGFR2-induced RAS/ERK activation, ectopic expression of sprouty (SPRY) family was reported in several kinds of cancers except gastric cancer. To explore the clinical significance of SPRY family and its correlation with FGFR2, we detected the expression of FGFR2 and SPRY family in 104 cases of gastric adenocarcinoma and subsequently analyzed their correlations with clinicopathological factors and overall survival rates by univariate and multivariate analysis...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994470/identification-of-feature-genes-for-smoking-related-lung-adenocarcinoma-based-on-gene-expression-profile-data
#14
Ying Liu, Ran Ni, Hui Zhang, Lijun Miao, Jing Wang, Wenqing Jia, Yuanyuan Wang
This study aimed to identify the genes and pathways associated with smoking-related lung adenocarcinoma. Three lung adenocarcinoma associated datasets (GSE43458, GSE10072, and GSE50081), the subjects of which included smokers and nonsmokers, were downloaded to screen the differentially expressed feature genes between smokers and nonsmokers. Based on the identified feature genes, we constructed the protein-protein interaction (PPI) network and optimized feature genes using closeness centrality (CC) algorithm...
2016: OncoTargets and Therapy
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/27988457/in-vitro-and-in-vivo-activity-of-lucitanib-in-fgfr1-2-amplified-or-mutated-cancer-models
#16
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/27966449/association-between-fgfr2-rs2981582-rs2420946-and-rs2981578-polymorphism-and-breast-cancer-susceptibility-a-meta-analysis
#17
Yafei Zhang, Xianling Zeng, Pengdi Liu, Ruofeng Hong, Hongwei Lu, Hong Ji, Le Lu, Yiming Li
The association between fibroblast growth factor receptor 2 (FGFR2) polymorphism and breast cancer (BC) susceptibility remains inconclusive. The purpose of this systematic review was to evaluate the relationship between FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphism and BC risk. PubMed, Web of science and the Cochrane Library databases were searched before October 11, 2015 to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27933954/discovery-of-5-amino-1-2-methyl-3h-benzimidazol-5-yl-pyrazol-4-yl-1h-indol-2-yl-methanone-ch5183284-debio-1347-an-orally-available-and-selective-fibroblast-growth-factor-receptor-fgfr-inhibitor
#18
Hirosato Ebiike, Naoki Taka, Masayuki Matsushita, Masayuki Ohmori, Kyoko Takami, Ikumi Hyohdoh, Masami Kohchi, Tadakatsu Hayase, Hiroki Nishii, Kenji Morikami, Yoshito Nakanishi, Nukinori Akiyama, Hidetoshi Shindoh, Nobuya Ishii, Takehito Isobe, Hiroharu Matsuoka
The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases regulates multiple biological processes, such as cell proliferation, migration, apoptosis, and differentiation. Various genetic alterations that drive activation of the receptors and the pathway are associated with tumor growth and survival; therefore, the FGFR family represents an attractive therapeutic target for treating cancer. Here, we report the discovery and the pharmacological profiles of 8 (CH5183284/Debio 1347), an orally available and selective inhibitor of FGFR1, FGFR2, and FGFR3...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27927983/a-new-method-to-study-heterodimerization-of-membrane-proteins-and-its-application-to-fibroblast-growth-factor-receptors
#19
Nuala Del Piccolo, Sarvenaz Sarabipour, Kalina Hristova
The activity of receptor tyrosine kinases (RTKs) is controlled through their lateral dimerization in the plasma membrane. RTKs are believed to form both homodimers and heterodimers, and the different dimers are believed to play unique roles in cell signaling. However, RTK heterodimers remain poorly characterized, as compared to homodimers, due to limitations in current experimental methods. Here, we develop a Förster Resonance Energy Transfer (FRET)-based methodology to assess the thermodynamics of hetero-interactions in the plasma membrane...
December 7, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27919550/corrigendum-to-targeting-fgfr2-with-alofanib-rpt835-shows-potent-activity-in-tumour-models-eur%C3%A2-j%C3%A2-cancer-61-2016-20-28
#20
Ilya Tsimafeyeu, John Ludes-Meyers, Evgenia Stepanova, Frits Daeyaert, Dmitry Khochenkov, Jean-Baptiste Joose, Eliso Solomko, Koen Van Akene, Nina Peretolchina, Wei Yin, Oxana Ryabaya, Mikhail Byakhov, Sergei Tjulandin
No abstract text is available yet for this article.
January 2017: European Journal of Cancer
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