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https://www.readbyqxmd.com/read/28814615/single-cell-gene-expression-of-the-bovine-blastocyst
#1
Veronica M Negrón-Pérez, Yanping Zhang, Peter J Hansen
The first two differentiation events in the blastocyst result in three cell types - epiblast, trophectoderm (TE), and hypoblast. The purpose here was to identify molecular markers for each cell type in the bovine and evaluate differences in gene expression among individual cells of each lineage. The cDNA from 67 individual cells from dissociated blastocysts was used to determine transcript abundance for 96 genes implicated as cell lineage markers in other species or potentially involved in developmental processes...
August 16, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28802831/validation-of-a-targeted-rna-sequencing-assay-for-kinase-fusion-detection-in-solid-tumors
#2
Julie W Reeser, Dorrelyn Martin, Jharna Miya, Esko A Kautto, Ezra Lyon, Eliot Zhu, Michele R Wing, Amy Smith, Matthew Reeder, Eric Samorodnitsky, Hannah Parks, Karan R Naik, Joseph Gozgit, Nicholas Nowacki, Kurtis D Davies, Marileila Varella-Garcia, Lianbo Yu, Aharon G Freud, Joshua Coleman, Dara L Aisner, Sameek Roychowdhury
Kinase gene fusions are important drivers of oncogenic transformation and can be inhibited with targeted therapies. Clinical grade diagnostics using RNA sequencing to detect gene rearrangements in solid tumors are limited, and the few that are available require prior knowledge of fusion break points. To address this, we have analytically validated a targeted RNA sequencing assay (OSU-SpARKFuse) for fusion detection that interrogates complete transcripts from 93 kinase and transcription factor genes. From a total of 74 positive and 36 negative control samples, OSU-SpARKFuse had 93...
August 8, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28796141/therapeutic-potential-for-fgfr-inhibitors-in-sox9-fgfr2-coexpressing-pancreatic-cancer
#3
Hazel OʼSullivan, Fergal C Kelleher, Máire Lavelle, Brianan McGovern, Jean Murphy, Niall Swan, Ray McDermott
No abstract text is available yet for this article.
September 2017: Pancreas
https://www.readbyqxmd.com/read/28790902/integration-of-brain-and-skull-in-prenatal-mouse-models-of-apert-and-crouzon-syndromes
#4
Susan M Motch Perrine, Tim Stecko, Thomas Neuberger, Ethylin W Jabs, Timothy M Ryan, Joan T Richtsmeier
The brain and skull represent a complex arrangement of integrated anatomical structures composed of various cell and tissue types that maintain structural and functional association throughout development. Morphological integration, a concept developed in vertebrate morphology and evolutionary biology, describes the coordinated variation of functionally and developmentally related traits of organisms. Syndromic craniosynostosis is characterized by distinctive changes in skull morphology and perceptible, though less well studied, changes in brain structure and morphology...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28776573/pancreatic-intraductal-tubulopapillary-neoplasm-is-genetically-distinct-from-intraductal-papillary-mucinous-neoplasm-and-ductal-adenocarcinoma
#5
Olca Basturk, Michael F Berger, Hiroshi Yamaguchi, Volkan Adsay, Gokce Askan, Umesh K Bhanot, Ahmet Zehir, Fatima Carneiro, Seung-Mo Hong, Giuseppe Zamboni, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Serdar Balci, Peter Allen, Naoki Ikari, Shoko Takeuchi, Hiroyuki Akagawa, Atsushi Kanno, Tooru Shimosegawa, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Ryota Higuchi, Masakazu Yamamoto, Kyoko Shimizu, Toru Furukawa, David S Klimstra
Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28768473/a-de-novo-missense-mutation-of-fgfr2-causes-facial-dysplasia-syndrome-in-holstein-cattle
#6
Jørgen S Agerholm, Fintan J McEvoy, Steffen Heegaard, Carole Charlier, Vidhya Jagannathan, Cord Drögemüller
BACKGROUND: Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. RESULTS: Seven malformed calves were submitted examination...
August 2, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28762674/identifying-genetic-sources-of-phenotypic-heterogeneity-in-orofacial-clefts-by-targeted-sequencing
#7
Jenna C Carlson, Margaret A Taub, Eleanor Feingold, Terri H Beaty, Jeffrey C Murray, Mary L Marazita, Elizabeth J Leslie
BACKGROUND: Orofacial clefts (OFCs), including nonsyndromic cleft lip with or without cleft palate (NSCL/P), are common birth defects. NSCL/P is highly heterogeneous with multiple phenotypic presentations. Two common subtypes of NSCL/P are cleft lip (CL) and cleft lip with cleft palate (CLP) which have different population prevalence. Similarly, NSCL/P can be divided into bilateral and unilateral clefts, with unilateral being the most common. Individuals with unilateral NSCL/P are more likely to be affected on the left side of the upper lip, but right side affection also occurs...
July 17, 2017: Birth defects research
https://www.readbyqxmd.com/read/28757702/clinical-characteristics-of-crouzon-syndrome
#8
L Balyen, L S Deniz Balyen, S Pasa
Crouzon syndrome (CS) is an genetic disorder with autosomal dominant inheritance caused by mutation of the gene for fibroblast growth factor receptor 2 (FGFR2) was described as one of the varieties of craniosynostosis. In this presented case, premature closure of the sutures had caused restricted skull growth and lack of space for the growing brain resulted to shallowed eyes and cranial and ophthalmic deformities and impairment in tooth development. Management of a patient of CS has two components. First is the release of prematurely fused sutures based on evidence of raised intracranial pressure...
May 2017: Oman Journal of Ophthalmology
https://www.readbyqxmd.com/read/28757654/predicting-triple-negative-breast-cancer-subtype-using-multiple-single-nucleotide-polymorphisms-for-breast-cancer-risk-and-several-variable-selection-methods
#9
Lothar Häberle, Alexander Hein, Matthias Rübner, Michael Schneider, Arif B Ekici, Paul Gass, Arndt Hartmann, Rüdiger Schulz-Wendtland, Matthias W Beckmann, Wing-Yee Lo, Werner Schroth, Hiltrud Brauch, Peter A Fasching, Marius Wunderle
INTRODUCTION: Studies of triple-negative breast cancer have recently been extending the inclusion criteria and incorporating additional molecular markers into the selection criteria, opening up scope for targeted therapies. The screening phases required for studies of this type are often prolonged, since the process of determining the molecular subtype and carrying out additional biomarker assessment is time-consuming. Parameters such as germline genotypes capable of predicting the molecular subtype before it becomes available from pathology might be helpful for treatment planning and optimizing the timing and cost of screening phases...
June 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28757652/genetic-breast-cancer-susceptibility-variants-and-prognosis-in-the-prospectively-randomized-success-a-study
#10
A Hein, B Rack, L Li, A B Ekici, A Reis, M P Lux, J M Cunningham, M Rübner, B L Fridley, A Schneeweiss, H Tesch, W Lichtenegger, T Fehm, G Heinrich, M Rezai, M W Beckmann, W Janni, R M Weinshilboum, L Wang, P A Fasching, L Häberle
Large-scale genotyping studies have identified over 70 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge regarding genetic risk factors associated with the prognosis is limited. The aim of this study was therefore to investigate the prognostic effect of nine known breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant, randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1) , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) , rs6504950 (COX11) ...
June 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28756492/large-scale-comprehensive-immunohistochemical-biomarker-analyses-in-esophageal-squamous-cell-carcinoma
#11
Ken Hatogai, Satoshi Fujii, Takashi Kojima, Hiroyuki Daiko, Shogo Nomura, Toshihiko Doi, Shigehisa Kitano, Atsushi Ohtsu, Yuichi Takiguchi, Takayuki Yoshino, Atsushi Ochiai
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease in the sense that the biological behavior is regulated by the activation of various signaling pathways. The aim of this study was to investigate the relationships between the expressions of various targetable proteins and the clinicopathological characteristics of ESCC patients. METHODS: A total of 286 patients with ESCC who had undergone curative surgical resection without neoadjuvant therapy were enrolled in this study...
July 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28736630/current-biologics-for-treatment-of-biliary-tract-cancers
#12
REVIEW
Diana Y Zhao, Kian-Huat Lim
Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28735443/retinoic-acid-regulates-avian-lung-branching-through-a-molecular-network
#13
Hugo Fernandes-Silva, Patrícia Vaz-Cunha, Violina Baranauskaite Barbosa, Carla Silva-Gonçalves, Jorge Correia-Pinto, Rute Silva Moura
Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development...
July 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28734796/clonal-composition-of-human-ovarian-cancer-based-on-copy-number-analysis-reveals-a-reciprocal-relation-with-oncogenic-mutation-status
#14
Kazuko Sakai, Masayo Ukita, Jeanette Schmidt, Longyang Wu, Marco A De Velasco, Alan Roter, Luis Jevons, Kazuto Nishio, Masaki Mandai
Intratumoral heterogeneity of cancer cells remains largely unexplored. Here we investigated the composition of ovarian cancer and its biological relevance. A whole-genome single nucleotide polymorphism array was applied to detect the clonal composition of 24 formalin-fixed, paraffin-embedded samples of human ovarian cancer. Genome-wide segmentation data consisting of the log2 ratio (log2R) and B allele frequency (BAF) were used to calculate an estimate of the clonal composition number (CC number) for each tumor...
July 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28711945/the-molecular-characterization-of-porcine-egg-precursor-cells
#15
Te-Sha Tsai, Jacqueline Johnson, Yvonne White, Justin C St John
Female-factor infertility can be caused by poor oocyte quality and depleted ovarian reserves. Egg precursor cells (EPCs), isolated from the ovarian cortex, have the potential to be used to overcome female infertility. We aimed to define the origins of EPCs by analyzing their gene expression profiles and mtDNA content using a mini-pig model. We characterized FAC-sorted DDX4+-derived porcine EPCs by performing RNA-sequencing and determined that they utilize pathways important for cell cycle and proliferation, which supports the existence of adult mitotically active oogonial cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687204/optimization-of-1h-indazol-3-amine-derivatives-as-potent-fibroblast-growth-factor-receptor-inhibitors
#16
Jing Cui, Xia Peng, Dingding Gao, Yang Dai, Jing Ai, Yingxia Li
Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4...
June 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28675510/the-co-regulatory-networks-of-tumor-suppressor-genes-oncogenes-and-mirnas-in-colorectal-cancer
#17
Martha L Slattery, Jennifer S Herrick, Lila E Mullany, Wade S Samowitz, John R Sevens, Lori Sakoda, Roger K Wolff
Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC and normal mucosa and evaluate how TSGs and OGs are associated with miRNAs. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were used. We focus on genes most strongly associated with CRC (fold change (FC) of ≥1...
July 4, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28674664/recombinant-expression-in-e-coli-of-human-fgfr2-with-its-transmembrane-and-extracellular-domains
#18
Adam Bajinting, Ho Leung Ng
Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases containing three domains: an extracellular receptor domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. FGFRs are activated by fibroblast growth factors (FGFs) as part of complex signal transduction cascades regulating angiogenesis, skeletal formation, cell differentiation, proliferation, cell survival, and cancer. We have developed the first recombinant expression system in E. coli to produce a construct of human FGFR2 containing its transmembrane and extracellular receptor domains...
2017: PeerJ
https://www.readbyqxmd.com/read/28667006/whole-genome-and-epigenomic-landscapes-of-etiologically-distinct-subtypes-of-cholangiocarcinoma
#19
Apinya Jusakul, Ioana Cutcutache, Chern Han Yong, Jing Quan Lim, Mi Ni Huang, Nisha Padmanabhan, Vishwa Nellore, Sarinya Kongpetch, Alvin Wei Tian Ng, Ley Moy Ng, Su Pin Choo, Swe Swe Myint, Raynoo Thanan, Sanjanaa Nagarajan, Weng Khong Lim, Cedric Chuan Young Ng, Arnoud Boot, Mo Liu, Choon Kiat Ong, Vikneswari Rajasegaran, Stefanus Lie, Alvin Soon Tiong Lim, Tse Hui Lim, Jing Tan, Jia Liang Loh, John R McPherson, Narong Khuntikeo, Vajaraphongsa Bhudhisawasdi, Puangrat Yongvanit, Sopit Wongkham, Yasushi Totoki, Hiromi Nakamura, Yasuhito Arai, Satoshi Yamasaki, Pierce K H Chow, Alexander Yaw Fui Chung, London Lucien Peng Jin Ooi, Kiat Hon Lim, Simona Dima, Dan G Duda, Irinel Popescu, Philippe Broet, Sen-Yung Hsieh, Ming-Chin Yu, Aldo Scarpa, Jiaming Lai, Di-Xian Luo, Andre Lopes Carvalho, André Luiz Vettore, Hyungjin Rhee, Young Nyun Park, Ludmil Alexandrov, Raluca Gordan, Steven G Rozen, Tatsuhiro Shibata, Chawalit Pairojkul, Bin Tean Teh, Patrick Tan
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke-Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements...
June 30, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28650109/inducible-activation-of-fgfr2-in-adult-mice-promotes-bone-formation-after-bone-marrow-ablation
#20
Wei Xu, Fengtao Luo, Quan Wang, Qiaoyan Tan, Junlan Huang, Siru Zhou, Zuqiang Wang, Xianding Sun, Liang Kuang, Min Jin, Nan Su, Wanling Jiang, Liang Chen, Huabing Qi, Ying Zhu, Bo Chen, Hangang Chen, Shuai Chen, Yu Gao, Xiaoling Xu, Chuxia Deng, Lin Chen, Yangli Xie, Xiaolan Du
Apert syndrome is one of the most severe craniosynostoses, resulting from gain-of-function mutations in fibroblast growth factor receptor 2 (FGFR2). Previous studies have shown that gain-of-function mutations of FGFR2 (S252W or P253R) cause skull malformation of human Apert syndrome by affecting both chondrogenesis and osteogenesis, underscoring the key role of FGFR2 in bone development. However, the effects of FGFR2 on bone formation at the adult stage have not been fully investigated. To investigate the role of FGFR2 in bone formation, we generated mice with tamoxifen-inducible expression of mutant FGFR2 (P253R) at the adult stage...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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