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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
#1
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.
December 3, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27914362/an-overview-of-the-binding-models-of-fgfr-tyrosine-kinases-in-complex-with-small-molecule-inhibitors
#2
REVIEW
Weiyan Cheng, Mixiang Wang, Xin Tian, Xiaojian Zhang
The fibroblast growth factor receptor (FGFR) family receptor tyrosine kinase (RTK) includes four structurally related members, termed as FGFR1, FGFR2, FGFR3, and FGFR4. Given its intimate role in the progression of several solid tumors, excessive FGFR signaling provides an opportunity for anticancer therapy. Along with extensive pharmacological studies validating the therapeutic potential of targeting the FGFRs for cancer treatment, co-crystal structures of FGFRs/inhibitors are continuously coming up to study the mechanism of actions and explore new inhibitors...
November 25, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27913571/snord126-promotes-hcc-and-crc-cell-growth-by-activating-the-pi3k-akt-pathway-through-fgfr2
#3
Xianlong Fang, Dongmei Yang, Hongping Luo, Shuai Wu, Wenjie Dong, Jing Xiao, Sujing Yuan, Aimin Ni, Kang-Jian Zhang, Xin-Yuan Liu, Liang Chu
Small nucleolar RNA (snoRNA) dysfunctions have been associated with cancer development. SNORD126 is an orphan C/D box snoRNA that is encoded within introns 5-6 of its host gene, cyclin B1-interacting protein 1 (CCNB1IP1) The cancer-associated molecular mechanisms triggered by SNORD126 are not fully understood. Here, we demonstrate that SNORD126 is highly expressed in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) patient samples. SNORD126 increased Huh-7 and SW480 cell growth and tumorigenicity in nude mice...
December 2, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27903959/genome-wide-haplotype-association-study-identify-the-fgfr2-gene-as-a-risk-gene-for-acute-myeloid-leukemia
#4
Hongchao Lv, Mingming Zhang, Zhenwei Shang, Jin Li, Shanshan Zhang, Duan Lian, Ruijie Zhang
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, and generally considered to be caused by environment and genetic factors. In this study, we combined a genome-wide haplotype association study (GWHAS) and gene prioritization strategy to mine AML-related genetic affect factors and understand its pathogenesis. A total of 175 AML patients were downloaded from the public GEO database (GSE32462) and 218 matched Caucasian controls were from the HapMap Project. We first identified the linkage disequilibrium (LD) blocks and performed a GWHAS to scan AML-related haplotypes...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892934/treatment-with-fgfr2-iiic-monoclonal-antibody-suppresses-weight-gain-and-adiposity-in-kka-y-mice
#5
K Nonogaki, T Kaji, T Yamazaki, Mari Murakami
Expression of β-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c, which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim of the present study was to determine the role of FGFR2c in the development of obesity and diabetes in KKA(y) mice. Treatment with mouse monoclonal FGFR2-IIIc antibody (0.5 mg kg(-1)) significantly suppressed body weight gain and epididymal white adipose tissue weight in individually housed KKA(y) mice while having no effect on daily food intake. In addition, treatment with FGFR2-IIIc antibody significantly increased plasma-free fatty acid levels while having no effect on blood glucose or plasma FGF21 levels...
November 28, 2016: Nutrition & Diabetes
https://www.readbyqxmd.com/read/27891566/sudden-death-associated-with-syndromic-craniosynostosis
#6
Alžbeta Ginelliová, Daniel Farkaš, Silvia Farkašová Iannaccone, Vlasta Vyhnálková, Peter Vasovčák
In this paper we report the autopsy findings of a 7 year old girl who presented with headache, nausea and repeated vomiting and died unexpectedly at home. She had no previous history of major illnesses and no history of epileptic seizures. External examination revealed ocular abnormalities. Internal examination demonstrated severe cerebral edema with tonsillar herniation, premature fusion of the cranial bone sutures, and prominent convolutional markings of the inner table of the skull. Death was due to severe cerebral edema complicating syndromic craniosynostosis...
November 28, 2016: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/27872721/the-role-of-fibroblast-growth-factor-receptor-2-fgfr2-in-differentiation-of-bovine-spermatogonial-stem-cells-scc
#7
Rahem Khoshbakht, Mohammad Tabatabaei, Saeid Hoseinzadeh, Mojtaba Mojtaba, Hesamaddin Shirzad Aski, Enayat Berizi
Although poultry meat is considered as the main source for human Campylobacter infections, there is limited information about non-poultry sources. The present study was aimed to investigate the prevalence and the antibiotic resistance of thermophilic Campylobacter spp. in fecal samples of the cattle and sheep in Shiraz, Iran. A total of 302 fecal samples were obtained from clinically healthy, slaughtered cattle and sheep from Shiraz slaughterhouse. The animals were clinically healthy before being slaughtered...
2016: Veterinary Research Forum
https://www.readbyqxmd.com/read/27870215/detangling-the-evolutionary-developmental-integration-of-dentate-jaws-evidence-that-a-p63-gene-network-regulates-odontogenesis-exclusive-of-mandible-morphogenesis
#8
Muhammad T Raj, Julia C Boughner
Vertebrate jaws and dentitions fit and function together, yet the genetic processes that coordinate cranial and dental morphogenesis and evolution remain poorly understood. Teeth but not jaws fail to form in the edentate p63(-/-) mouse mutant, which we used here to identify genes important to odontogenesis, but not jaw morphogenesis, and that may allow dentitions to change during development and evolution without necessarily affecting the jaw skeleton. With the working hypothesis that tooth and jaw development are autonomously controlled by discreet gene regulatory networks, using gene expression microarray assays validated by quantitative reverse-transcription PCR we contrasted expression in mandibular prominences at embryonic days (E) 10-13 of mice with normal lower jaw development but either normal (p63(+/-) , p63(+/+) ) or arrested (p63(-/-) ) tooth development...
December 2016: Evolution & Development
https://www.readbyqxmd.com/read/27852068/fibroblast-growth-factor-signalling-induces-loss-of-progesterone-receptor-in-breast-cancer-cells
#9
Dominika Piasecka, Kamila Kitowska, Dominika Czaplinska, Kamil Mieczkowski, Magdalena Mieszkowska, Lukasz Turczyk, Andrzej C Skladanowski, Anna J Zaczek, Wojciech Biernat, Radzislaw Kordek, Hanna M Romanska, Rafal Sadej
We have recently demonstrated that, fibroblast growth factor 2 (FGFR2), signalling via ribosomal S6 kinase 2 (RSK2), promotes progression of breast cancer (BCa). Loss of progesterone receptor (PR), whose activity in BCa cells can be stimulated by growth factor receptors (GFRs), is associated with poor patient outcome. Here we showed that FGF7/FGFR2 triggered phosphorylation of PR at Ser294, PR ubiquitination and subsequent receptor`s degradation via the 26S proteasome pathway in BCa cells. We further demonstrated that RSK2 mediated FGF7/FGFR2-induced PR downregulation...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848153/previous-gwas-hits-in-relation-to-young-onset-breast-cancer
#10
Min Shi, Katie M O'Brien, Dale P Sandler, Jack A Taylor, Dmitri V Zaykin, Clarice R Weinberg
PURPOSE: Genome-wide association studies (GWAS) have identified dozens of single-nucleotide polymorphisms (SNPs) associated with breast cancer. Few studies focused on young-onset breast cancer, which exhibits etiologic and tumor-type differences from older-onset disease. Possible confounding by prenatal effects of the maternal genome has also not been considered. METHODS: Using a family-based design for breast cancer before age 50, we assessed the relationship between breast cancer and 77 GWAS-identified breast cancer risk SNPs...
November 15, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27829278/systemic-therapy-for-biliary-cancers
#11
Emmet Jordan, Ghassan K Abou-Alfa, Maeve A Lowery
Biliary tract cancers represent an uncommon, heterogenous malignant group of tumors that include gallbladder cancers (GBC) and cholangiocarcinomas that are frequently detected in the locally advanced or metastatic setting. The randomized phase III ABC-02 trial established the combination regimen of cisplatin plus gemcitabine as standard of care therapy. Nevertheless, despite prior and subsequent attempts utilizing a variety of treatment strategies clinical outcomes for these cancers remains disappointing, necessitating the innate call for improvements in treatment approaches...
October 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/27829009/the-morphogenesis-of-cranial-sutures-in-zebrafish
#12
Jolanta M Topczewska, Ramy A Shoela, Joanna P Tomaszewski, Rupa B Mirmira, Arun K Gosain
Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone...
2016: PloS One
https://www.readbyqxmd.com/read/27821131/frequency-of-egfr-t790m-mutation-and-multimutational-profiles-of-rebiopsy-samples-from-non-small-cell-lung-cancer-developing-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors-in-japanese-patients
#13
Ryo Ko, Hirotsugu Kenmotsu, Masakuni Serizawa, Yasuhiro Koh, Kazushige Wakuda, Akira Ono, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Mitsuhiro Isaka, Masahiro Endo, Takashi Nakajima, Yasuhisa Ohde, Nobuyuki Yamamoto, Kazuhisa Takahashi, Toshiaki Takahashi
BACKGROUND: The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. METHODS: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27812884/alofanib-an-allosteric-fgfr2-inhibitor-has-potent-effects-on-ovarian-cancer-growth-in-preclinical-studies
#14
Alexandra Tyulyandina, Daniel Harrison, Wei Yin, Evgenia Stepanova, Dmitry Kochenkov, Eliso Solomko, Nina Peretolchina, Frits Daeyaert, Jean-Baptiste Joos, Koen Van Aken, Mikhail Byakhov, Evgenia Gavrilova, Sergei Tjulandin, Ilya Tsimafeyeu
Purpose Early data suggest that combining FGFR2 inhibitors with platinum-containing cytotoxic agents for the treatment of epithelial ovarian cancer may yield increased antitumor activity. We investigated antitumor activity of alofanib (RPT835), a novel allosteric FGFR2 inhibitor, in ovarian cancer in vitro and in vivo. Methods Equal amounts of ovarian cancer cell (SKOV3) lysates were analyzed for FGFR1-3 protein expression using Wes. To assess the efficacy of alofanib on FGF-mediated cell proliferation, SKOV3 cells were incubated and were treated with serially diluted alofanib...
November 3, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27812792/polymorphous-low-grade-neuroepithelial-tumor-of-the-young-plnty-an-epileptogenic-neoplasm-with-oligodendroglioma-like-components-aberrant-cd34-expression-and-genetic-alterations-involving-the-map-kinase-pathway
#15
Jason T Huse, Matija Snuderl, David T W Jones, Carole D Brathwaite, Nolan Altman, Ehud Lavi, Richard Saffery, Alexandra Sexton-Oates, Ingmar Blumcke, David Capper, Matthias A Karajannis, Ryma Benayed, Lukas Chavez, Cheddhi Thomas, Jonathan Serrano, Laetitia Borsu, Marc Ladanyi, Marc K Rosenblum
Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population...
November 3, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27803855/fgfr2-mutation-in-a-chinese-family-with-unusual-crouzon-syndrome
#16
Zi-Li Li, Xue Chen, Wen-Juan Zhuang, Wei Zhao, Ya-Ni Liu, Fang-Xia Zhang, Ruo-Shui Ha, Jin-Hua Wu, Chen Zhao, Xun-Lun Sheng
AIM: To describe the clinical characteristics with genetic lesions in a Chinese family with Crouzon syndrome. METHODS: All five patients from this family were included and received comprehensive ophthalmic and systemic examinations. Direct sequencing of the FGFR2 gene was employed for mutation identification. Crystal structure analysis was applied to analyze the structural changes associated with the substitution. RESULTS: All patients presented typical Crouzon features, including short stature, craniosynostosis, mandibular prognathism, shallow orbits with proptosis, and exotropia...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27802183/prognostic-impact-of-fibroblast-growth-factor-receptor-2-gene-amplification-in-patients-receiving-fluoropyrimidine-and-platinum-chemotherapy-for-metastatic-and-locally-advanced-unresectable-gastric-cancers
#17
Seyoung Seo, Seong Joon Park, Min-Hee Ryu, Sook Ryun Park, Baek-Yeol Ryoo, Young Soo Park, Young-Soon Na, Chae-Won Lee, Ju-Kyung Lee, Yoon-Koo Kang
Although Fibroblast growth factor receptor (FGFR) 2 gene amplification and its prognostic significance have been reported in resectable gastric cancers, information on these features remains limited in the metastatic setting. The presence of FGFR2 amplification was assessed in formalin-fixed, paraffin-embedded tissues using a quantitative PCR-based gene copy number assay with advanced gastric cancer cohorts. A total of 327 patients with tumor portion of ≥70% were analyzed for clinical features. Among these patients, 260 who received first-line fluoropyrimidine and platinum chemotherapy were analyzed for survival...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27785367/fgfr1-2-and-3-protein-overexpression-and-molecular-aberrations-of-fgfr3-in-early-stage-non-small-cell-lung-cancer
#18
Willemijn Sme Theelen, Lorenza Mittempergher, Stefan M Willems, Astrid J Bosma, Dennis Dgc Peters, Vincent van der Noort, Eva J Japenga, Ton Peeters, Koos Koole, Tonći Šuštić, J L Blaauwgeers, Carel J van Noesel, René Bernards, Michel M van den Heuvel
This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3-TACC3 translocation and FGFR3 amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC)) were analysed with immunohistochemistry (IHC) for expression of FGFR1, 2 and 3. Expression levels of FGFR1, 2 and 3 were correlated with clinicopathological features...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27779515/frequent-coamplification-of-receptor-tyrosine-kinase-and-downstream-signaling-genes-in-japanese-primary-gastric-cancer-and-conversion-in-matched-lymph-node-metastasis
#19
Arnaldo N S Silva, Jordy Coffa, Varsha Menon, Lindsay C Hewitt, Kakoli Das, Yohei Miyagi, Dan Bottomley, Hayley Slaney, Toru Aoyama, Wolfram Mueller, Tomio Arai, Iain B Tan, Niantao Deng, Xiu B Chan, Patrick Tan, Akira Tsuburaya, Kentaro Sakamaki, Jeremy D Hayden, Takaki Yoshikawa, Ilse Zondervan, Suvi Savola, Heike I Grabsch
OBJECTIVE: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). BACKGROUND: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. METHODS: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status...
October 24, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27764800/gwas-in-the-signal-phare-clinical-cohort-restricts-the-association-between-the-fgfr2-locus-and-estrogen-receptor-status-to-her2-negative-breast-cancer-patients
#20
David G Cox, Elsa Curtit, Gilles Romieu, Pierre Fumoleau, Maria Rios, Hervé Bonnefoi, Thomas Bachelot, Patrick Soulié, Christelle Jouannaud, Hugues Bourgeois, Thierry Petit, Isabelle Tennevet, David Assouline, Marie-Christine Mathieu, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Ariane Darut-Jouve, Jean-Marc Ferrero, Carole Tarpin, Christelle Lévy, Valérie Delecroix, Véronique Trillet-Lenoir, Oana Cojocarasu, Jérôme Meunier, Jean-Yves Pierga, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Jean-François Deleuze, Iris Pauporté, Gilles Thomas, Xavier Pivot
Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1...
October 14, 2016: Oncotarget
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