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https://www.readbyqxmd.com/read/28634123/clinical-utility-of-chromosomal-aneusomy-in-individuals-at-high-risk-of-lung-cancer
#1
Anna E Barón, Severine Kako, William J Feser, Heather Malinowski, Daniel Merrick, Kavita Garg, Stephen Malkoski, Shannon Pretzel, Jill M Siegfried, Wilbur A Franklin, York Miller, Holly J Wolf, Marileila Varella-Garcia
INTRODUCTION: Low dose CT screening for lung cancer has a high false positive rate with frequent discovery of indeterminate pulmonary nodules. Noninvasive biomarkers are needed to reduce false positives and improve risk stratification. A retrospective longitudinal evaluation was performed to assess chromosomal aneusomy in sputum via fluorescence in situ hybridization (CA-FISH) in four nested case-control studies. METHODS: ROC analysis resulted in two grouped cohorts: High Risk (CO High Risk and CO Nodule; 68 Cases, 69 controls) and Screening (ACRIN/NLST and PLuSS; 97 Cases, 185 controls)...
June 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28630457/how-impaired-efficacy-happened-between-gancao-and-yuanhua-compounds-targets-and-pathways
#2
Jin-Gao Yu, Jianming Guo, Kevin Yue Zhu, Weiwei Tao, Yanyan Chen, Pei Liu, Yongqing Hua, Yuping Tang, Jin-Ao Duan
As recorded in Traditional Chinese Medicine (TCM) theory, Gancao (Glycyrrhizae Radix et Rhizoma) could weaken the pharmacological effect or increase the toxicity of Yuanhua (Genkwa Flos). However, the theory has been suspected due to lack of evidence. Here, we investigate whether Gancao could weaken Yuanhua's diuretic effect, if so, which chemicals and which targets may be involved. Results showed that Yuanhua exerted diuretic effect through down-regulating renal AQP 2, without electrolyte disturbances such as K(+) loss which has been observed as side-effect of most diuretics...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630215/mechanisms-of-primary-drug-resistance-in-fgfr1-amplified-lung-cancer
#3
Florian Malchers, Meryem Seda Ercanoglu, Daniel Schütte, Roberta Castiglione, Verena Tischler, Sebastian Michels, Ilona Dahmen, Johannes Brägelmann, Roopika Menon, Johannes M Heuckmann, Julie George, Sascha Ansén, Martin L Sos, Alex Soltermann, Martin Peifer, Jurgen Wolf, Reinhard Büttner, Roman K Thomas
<br />The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single agent FGFR inhibition and several tumors exhibited insufficient tumor shrinkage, compatible with the existence of drug-resistant tumor cells...
June 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28621683/genomic-analysis-of-exceptional-responder-to-regorafenib-in-treatment-refractory-metastatic-rectal-cancer-a-case-report-and-review-of-the-literature
#4
Krittiya Korphaisarn, Jonathan M Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C Litzenburger, Ken Chen, Gordon B Mills, Dipen M Maru, Funda Meric-Bernstan, Kenna R Mills Shaw, Scott Kopetz
We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619752/the-met-axl-fgfr-inhibitor-s49076-impairs-aurora-b-activity-and-improves-the-antitumor-efficacy-of-radiotherapy
#5
Céline Clémenson, Cyrus Chargari, Winchygn Liu, Michele Mondini, Charles Ferté, Mike F Burbridge, Valérie Cattan, Anne Jacquet-Bescond, Eric Deutsch
Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefinitib in NSCLC patients whose tumors show resistance to EGFR inhibitors...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28615371/a-phase-1b-open-label-multicentre-study-of-azd4547-in-patients-with-advanced-squamous-cell-lung-cancers
#6
Paul K Paik, Ronglai Shen, Michael F Berger, David Ferry, Jean-Charles Soria, Alastair Mathewson, Claire Rooney, Neil R Smith, Marie Cullberg, Elaine Kilgour, Donal Landers, Paul Frewer, A Nigel Brooks, Fabrice André
Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in ~20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with anti-tumor activity in FGFR1 amplified SQCLC cell lines and patient-derived xenografts. <br /><br />Experimental Design: Based on these data, we performed a phase 1 study of AZD4547 in patients with previously treated stage IV FGFR1 amplified SQCLCs (NCT00979134)...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28614212/phosphaturic-mesenchymal-tumors-clinicopathologic-immunohistochemical-and-molecular-analysis-of-22-cases-expanding-their-morphologic-and-immunophenotypic-spectrum
#7
Abbas Agaimy, Michael Michal, Simion Chiosea, Fredrik Petersson, Ladislav Hadravsky, Glenn Kristiansen, Raymund E Horch, Jan Schmolders, Arndt Hartmann, Florian Haller, Michal Michal
Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm of uncertain histogenesis that has been linked to tumor-induced osteomalacia (TIO) since 1959. The neoplastic cells produce increased amount of FGF23 which results in TIO via uncontrolled renal loss of phosphate (phosphaturia), and consequently diminished bone mineralization. To date, ∼300 cases have been reported. Although there is increasing evidence that PMT can be diagnosed by reproducible histopathologic features, firm diagnosis has been often restricted to cases associated with TIO and, hence, diagnosis of "nonphosphaturic variants" remained challenging...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28611104/cisplatin-increases-sensitivity-to-fgfr-inhibition-in-patient-derived-xenograft-models-of-lung-squamous-cell-carcinoma
#8
Clare E Weeden, Aliaksei Z Holik, Richard J Young, Stephen B Ma, Jean-Marc Garnier, Stephen B Fox, Phillip Antippa, Louis B Irving, Daniel P Steinfort, Gavin M Wright, Prudence A Russell, Matthew E Ritchie, Christopher J Burns, Benjamin Solomon, Marie-Liesse Asselin-Labat
Lung squamous cell carcinoma (SqCC) is a molecularly complex and genomically unstable disease. No targeted therapy is currently approved for lung SqCC, although potential oncogenic drivers of SqCC have been identified, including amplification of the fibroblast growth factor receptor 1 (FGFR1). Reports from a recently completed clinical trial indicate low response rates in patients treated with FGFR tyrosine kinase inhibitors, suggesting inadequacy of FGFR1 amplification as a biomarker of response, or the need for combination treatment...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28599074/beyond-epithelial-to-mesenchymal-transition-common-suppression-of-differentiation-programs-underlies-epithelial-barrier-dysfunction-in-mild-moderate-and-severe-asthma
#9
Lucas F Loffredo, Hiam Abdala-Valencia, Kishore R Anekalla, Lyda Cuervo-Pardo, Cara J Gottardi, Sergejs Berdnikovs
BACKGROUND: Epithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood. METHODS: We used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes...
June 9, 2017: Allergy
https://www.readbyqxmd.com/read/28598150/high-yield-site-specific-conjugation-of-fibroblast-growth-factor-1-with-monomethylauristatin-e-via-cysteine-flanked-by-basic-residues
#10
Michal Lobocki, Malgorzata Zakrzewska, Anna Szlachcic, Mateusz Adam Krzyscik, Aleksandra Sokolowska-Wedzina, Jacek Otlewski
Site-specific conjugation is a leading trend in the development of protein conjugates, including antibody-drug conjugates (ADCs), suitable for targeted cancer therapy. Here, we present a very efficient strategy for specific attachment of a cytotoxic drug to fibroblast growth factor 1 (FGF1), a natural ligand of FGF receptors (FGFRs), which are overexpressed in several types of lung, breast and gastric cancers and are therefore an attractive molecular target. Recently we showed that FGF1 fused to monomethylauristatin E (vcMMAE) was highly cytotoxic to cells presenting FGFRs on their surface and could be used as a targeting agent alternative to an antibody...
June 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#11
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28583501/otorhinolaryngologic-manifestations-of-hartsfield-syndrome-case-series-and-review-of-literature
#12
Jeremie D Oliver, Deanna C Menapace, Shelagh A Cofer
Diagnosis of Hartsfield syndrome includes recognition of three distinct clinical anomalies: holoprosencephaly, ectrodactyly, and bilateral cleft-lip and palate syndrome. A family including three male siblings all affected by Hartsfield syndrome presented to our institution for care. An autosomal dominant variant in Fibroblast Growth Factor Receptor 1 (FGFR1) was identified. This report focuses on otorhinolaryngologic manifestationsof Hartsfield syndrome, previously undescribed, including midline defects of holoprosencephaly, bilateral cleft-lip and palate, retrognathia, gastroesophageal reflux disease, external ear anomalies, eustachian tube dysfunction, and midface abnormalities, in addition to multidisciplinary, long-term management strategies...
July 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28558758/fgf2-fgfr1-regulates-autophagy-in-fgfr1-amplified-non-small-cell-lung-cancer-cells
#13
Hong Yuan, Zi-Ming Li, Jiaxiang Shao, Wen-Xiang Ji, Weiliang Xia, Shun Lu
BACKGROUND: Autophagy is a conserved catabolic process to degrade cellular organelles. The role of autophagy in cancer development is complex. Amplification of fibroblast growth factor receptor 1 (FGFR1) is one of the most frequent targets in lung squamous cell carcinoma (SQCC). Whether fibroblast growth factor 2 (FGF2)/FGFR1 contributes to the regulation of autophagy remains elusive. METHODS: Autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3), formation of GFP-LC3 puncta, and monodansylcadaverine (MDC) staining...
May 30, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28554745/genomic-profiling-of-esophageal-squamous-cell-carcinoma-escc-basis-for-precision-medicine
#14
Jung Wook Yang, Yoon-La Choi
PURPOSE: Preparing for precision medicine, we surveyed genomic alterations in esophageal squamous cell carcinoma (ESCC) and identified candidate therapeutic targets by genomic profiling using next-generation sequencing (NGS). MATERIALS AND METHODS: Single-nucleotide variations, indels, and copy number variations in 80 genes were evaluated by targeted deep sequencing in 24 surgically resected ESCC specimens. Immunohistochemistry analyses and silver in situ hybridization for ERBB2 (HER2) were conducted to verify the NGS results...
February 28, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28552744/reduction-in-serum-fibroblast-growth-factor-21-after-gastric-bypass-is-related-to-changes-in-hepatic-fat-content
#15
Karen Fjeldborg, Steen B Pedersen, Holger J Møller, Bjørn Richelsen
BACKGROUND: Fibroblast growth factor 21 (FGF21) is elevated in obesity. OBJECTIVES: We investigated the circulating level of FGF21 and the expression of FGF21, beta-klotho (KLB), and FGF receptor 1 (FGFR1) in adipose tissue in relation to weight, fat distribution, and Roux-en-Y gastric bypass (RYGB)-induced weight loss. SETTING: The Department of Endocrinology at Aarhus University Hospital. METHODS: Thirty-one obese patients were enrolled...
April 7, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28552559/lineage-establishment-and-progression-within-the-inner-cell-mass-of-the-mouse-blastocyst-requires-fgfr1-and-fgfr2
#16
Minjung Kang, Vidur Garg, Anna-Katerina Hadjantonakis
Fibroblast growth factor 4 (FGF4) is the key signal driving specification of primitive endoderm (PrE) versus pluripotent epiblast (EPI) within the inner cell mass (ICM) of the mouse blastocyst. To gain insight into the receptor(s) responding to FGF4 within ICM cells, we combined single-cell-resolution quantitative imaging with single-cell transcriptomics of wild-type and Fgf receptor (Fgfr) mutant embryos. Despite the PrE-specific expression of FGFR2, it is FGFR1, expressed by all ICM cells, that is critical for establishment of a PrE identity...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28552557/distinct-requirements-for-fgfr1-and-fgfr2-in-primitive-endoderm-development-and-exit-from-pluripotency
#17
Andrei Molotkov, Pierre Mazot, J Richard Brewer, Ryan M Cinalli, Philippe Soriano
Activation of the FGF signaling pathway during preimplantation development of the mouse embryo is known to be essential for differentiation of the inner cell mass and the formation of the primitive endoderm (PrE). We now show using fluorescent reporter knockin lines that Fgfr1 is expressed in all cell populations of the blastocyst, while Fgfr2 expression becomes restricted to extraembryonic lineages, including the PrE. We further show that loss of both receptors prevents the development of the PrE and demonstrate that FGFR1 plays a more prominent role in this process than FGFR2...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28551702/alpha-7-nicotinic-receptor-signaling-pathway-participates-in-the-neurogenesis-induced-by-chat-positive-neurons-in-the-subventricular-zone
#18
Jianping Wang, Zhengfang Lu, Xiaojie Fu, Di Zhang, Lie Yu, Nan Li, Yufeng Gao, Xianliang Liu, Chunmao Yin, Junji Ke, Liyuan Li, Mengmeng Zhai, Shiwen Wu, Jiahong Fan, Liang Lv, Junchao Liu, Xuemei Chen, Qingwu Yang, Jian Wang
Choline acetyltransferase-positive (ChAT(+)) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine...
May 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28551329/myeloproliferative-neoplasms-with-t-8-22-p11-2-q11-2-bcr-fgfr1-a-meta-analysis-of-20-cases-shows-cytogenetic-progression-with-b-lymphoid-blast-phase
#19
Ximena Montenegro-Garreaud, Roberto N Miranda, Alexandra Reynolds, Guilin Tang, Sa A Wang, Mariko Yabe, Wei Wang, Lianghua Fang, Carlos E Bueso-Ramos, Pei Lin, L Jeffrey Medeiros, Xinyan Lu
Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of the FGFR1 is ZMYM2 and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with the FGFR1 and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia (CML) or very rarely, with B lymphoblastic leukemia (B-ALL)...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28545562/the-inhibition-of-fgf-receptor-1-activity-mediates-sorafenib-antiproliferative-effects-in-human-malignant-pleural-mesothelioma-tumor-initiating-cells
#20
Alessandra Pattarozzi, Elisa Carra, Roberto E Favoni, Roberto Würth, Daniela Marubbi, Rosa Angela Filiberti, Luciano Mutti, Tullio Florio, Federica Barbieri, Antonio Daga
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. METHODS: TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro...
May 25, 2017: Stem Cell Research & Therapy
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