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https://www.readbyqxmd.com/read/29038531/trpa1-fgfr2-binding-event-is-a-regulatory-oncogenic-driver-modulated-by-mirna-142-3p
#1
Jonathan Berrout, Eleni Kyriakopoulou, Lavanya Moparthi, Alexandra S Hogea, Liza Berrout, Cristina Ivan, Mihaela Lorger, John Boyle, Chris Peers, Stephen Muench, Jacobo Elies Gomez, Xin Hu, Carolyn Hurst, Thomas Hall, Sujanitha Umamaheswaran, Laura Wesley, Mihai Gagea, Michael Shires, Iain Manfield, Margaret A Knowles, Simon Davies, Klaus Suhling, Yurema Teijeiro Gonzalez, Neil Carragher, Kenneth Macleod, N Joan Abbott, George A Calin, Nikita Gamper, Peter M Zygmunt, Zahra Timsah
Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29027430/-virtual-screening-of-anti-angiogenesis-flavonoids-from-sophora-flavescens
#2
Xi-Xin Chen, Yi Liu, Rong Huang, Lin-Lin Zhao, Lei Chen, Shu-Mei Wang
Angiogenesis is a dynamic, multi-step process. It is known that about 70 diseases are related to angiogenesis. Both the experimental and the literature reports showed that Sophora flavescens inhibit angiogenesis significantly, but the material basis and the mechanism of action have not been clear. In this study, molecular docking was used for screening of anti-angiogenesis flavonoids from the roots of S. flavescens. One handred and twenty-six flavonoids selected from S. flavescens were screened in the docking ligand database with six targets(VEGF-a,TEK,KDR,Flt1,FGFR1 and FGFR2) as the receptors...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29019756/imaging-of-skeletal-disorders-caused-by-fibroblast-growth-factor-receptor-gene-mutations
#3
Kiran M Sargar, Achint K Singh, Simon C Kao
Fibroblast growth factors and fibroblast growth factor receptors (FGFRs) play important roles in human axial and craniofacial skeletal development. FGFR1, FGFR2, and FGFR3 are crucial for both chondrogenesis and osteogenesis. Mutations in the genes encoding FGFRs, types 1-3, are responsible for various skeletal dysplasias and craniosynostosis syndromes. Many of these disorders are relatively common in the pediatric population, and diagnosis is often challenging. These skeletal disorders can be classified based on which FGFR is affected...
October 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28985766/mutations-in-brca1-brca2-and-other-breast-and-ovarian-cancer-susceptibility-genes-in-central-and-south-american-populations
#4
REVIEW
Lilian Jara, Sebastian Morales, Tomas de Mayo, Patricio Gonzalez-Hormazabal, Valentina Carrasco, Raul Godoy
Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate- and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel...
October 6, 2017: Biological Research
https://www.readbyqxmd.com/read/28984303/analysis-of-clinically-relevant-somatic-mutations-in-high-risk-head-and-neck-cutaneous-squamous-cell-carcinoma
#5
Catherine Zilberg, Matthew Weicai Lee, Bing Yu, Bruce Ashford, Spiridoula Kraitsek, Marie Ranson, Kerwin Shannon, Mark Cowley, N Gopalakrishna Iyer, Carsten E Palme, Sydney Ch'ng, Tsu-Hui Hubert Low, Sandra O'Toole, Jonathan R Clark, Ruta Gupta
Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months...
October 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28981091/neuron-and-microglia-macrophage-derived-fgf10-activate-neuronal-fgfr2-pi3k-akt-signaling-and-inhibit-microglia-macrophages-tlr4-nf-%C3%AE%C2%BAb-dependent-neuroinflammation-to-improve-functional-recovery-after-spinal-cord-injury
#6
Jian Chen, Zhouguang Wang, ZengMing Zheng, Yu Chen, Sinan Khor, KeSi Shi, ZiLi He, Qingqing Wang, Yingzheng Zhao, Hongyu Zhang, Xiaokun Li, Jiawei Li, Jiayu Yin, Xiangyang Wang, Jian Xiao
Therapeutics used to treat central nervous system (CNS) injury were designed to repair neurites and inhibit cell apoptosis. Previous studies have shown that neuron-derived FGF10 exerts potential neuroprotective effects after cerebral ischemia injury. However, little is known about the role of endogenous FGF10 in the recovery process after spinal cord injury (SCI). In this study, we found that FGF10 is mainly produced by neuron and microglia/macrophages, and its expression is increased after SCI. Exogenous treatment of FGF10 improved functional recovery after injury by reducing apoptosis, as well as repairing neurites via FGFR2/PI3K/Akt pathway...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28980322/fibroblast-growth-factor-21-attenuates-calcification-of-vascular-smooth-muscle-cells-in%C3%A2-vitro
#7
Fangying Cao, Shaoping Wang, Xiangrong Cao, Xiaoxiao Liu, Kun Fu, Peng Hao, Jinghua Liu
OBJECTIVES: Vascular calcification is a dysfunction of the vasculature. Recent findings indicate that fibroblast growth factor21 (FGF21), a protector of the cardiovascular system, is related to the mineral deposition of bone and enhances the osteogenic activity of bone morphogenic protein (BMP)-2. In this study, we explored whether FGF21 suppresses vascular calcification. METHODS: A calcifying model was established by culturing primary rat vascular aortic smooth muscle cells (VSMCs) in a beta-glycerophosphate (BGP)-containing calcifying medium for 14 days...
October 4, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28978722/acquired-resistance-to-fgfr-inhibitor-in-diffuse-type-gastric-cancer-through-an-akt-independent-pkc-mediated-phosphorylation-of-gsk3%C3%AE
#8
Wen Min Lau, Eileen Teng, Kie Kyon Huang, Jin Wei Tan, Kakoli Das, Zhijiang Zang, Tania Chia, Ming Teh, Koji Kono, Wei Peng Yong, Asim Shabbir, Amy Tay, Niam Sin Phua, Patrick Tan, Shing Leng Chan, Jimmy Bok Yan So
Preclinical models of diffuse type gastric cancer (DGC) that reliably predict clinical activity of novel compounds are lacking. To overcome the problem of poor tumor cellularity in DGC, we used cells from malignant ascites to establish diffuse type gastric cancer patient-derived xenograft (PDX) models that recapitulate the primary cancer. Cells in PDX model GAGA6 with FGFR2 amplification were sensitive to AZD4547, a potent FGFR inhibitor that is being clinically evaluated for FGFR-aberrant cancer types. Intermittent in vivo treatment of GAGA6 tumors with AZD4547 gave rise to PDX tumors with acquired resistance to AZD4547, GAGA6-R...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28972963/a-phase-1-study-of-arq-087-an-oral-pan-fgfr-inhibitor-in-patients-with-advanced-solid-tumours
#9
K P Papadopoulos, B F El-Rayes, A W Tolcher, A Patnaik, D W Rasco, R D Harvey, P M LoRusso, J C Sachdev, G Abbadessa, R E Savage, T Hall, B Schwartz, Y Wang, J Kazakin, W L Shaib
BACKGROUND: ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D). METHODS: Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28969006/the-molecular-characterization-of-porcine-egg-precursor-cells
#10
Te-Sha Tsai, Jacqueline Johnson, Yvonne White, Justin C 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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963640/development-of-response-classifier-for-vascular-endothelial-growth-factor-receptor-vegfr-tyrosine-kinase-inhibitor-tki-in-metastatic-renal-cell-carcinoma
#11
Heounjeong Go, Mun Jung Kang, Pil-Jong Kim, Jae-Lyun Lee, Ji Y Park, Ja-Min Park, Jae Y Ro, Yong Mee Cho
Vascular endothelial growth factor receptor (VEGFR)-targeted therapy improved the outcome of metastatic renal cell carcinoma (mRCC) patients. However, a prediction of the response to VEGFR-tyrosine kinase inhibitor (TKI) remains to be elucidated. We aimed to develop a classifier for VEGFR-TKI responsiveness in mRCC patients. Among 101 mRCC patients, ones with complete response, partial response, or ≥24 weeks stable disease in response to VEGFR-TKI treatment were defined as clinical benefit group, whereas patients with <24 weeks stable disease or progressive disease were classified as clinical non-benefit group...
September 29, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28960585/loss-of-heterozygosity-and-uniparental-disomy-of-chromosome-region-10q23-3-26-3-in-glioblastoma
#12
Ekaterina A Alekseeva, Ekaterina B Kuznetsova, Alexander S Tanas, Evgeny V Prozorenko, Anton M Zaytsev, Mikhail I Kurzhupov, Olga N Kirsanova, Viktoria V Rudenko, Vladimir V Strelnikov, Dmitry V Zaletaev
Glioblastoma is the most frequent and aggressive brain tumor in the adult population. Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases. We have tested 124 glioblastoma samples for LOH by microsatellite analysis of the 10q23.3-26.3 region which contains the cancer related genes PTEN, FGFR2, MKI67, and MGMT. Then, a real-time quantitative microsatellite analysis (QuMA) was used to qualitatively estimate the change in copy number of this region in the samples with LOH...
September 27, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28953502/endometrial-cancers-harboring-mutated-fibroblast-growth-factor-receptor-2-protein-are-successfully-treated-with-a-new-small-tyrosine-kinase-inhibitor-in-an-orthotopic-mouse-model
#13
Sebastien Taurin, Chieh-Hsiang Yang, Maria Reyes, Sungpil Cho, Demetrius M Coombs, Elke A Jarboe, Theresa L Werner, C Matthew Peterson, Margit M Janát-Amsbury
OBJECTIVES: AL3818 (anlotinib) is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGFβ), and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3). This study evaluates the efficacy of AL3818 studying tumor regression in an orthotopic murine endometrial cancer model. METHODS: We tested the cytotoxicity of AL3818 on a panel of 7 human endometrial cancer cell lines expressing either wild-type or mutant FGFR2 and also assessed the in vivo antitumor efficacy in a murine, orthotopic AN3CA endometrial cancer model...
September 26, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28945843/next-generation-sequencing-ngs-of-cell-free-circulating-tumor-dna-and-tumor-tissue-in-patients-with-advanced-urothelial-cancer-a-pilot-assessment-of-concordance
#14
P C Barata, V S Koshkin, P Funchain, D Sohal, A Pritchard, S Klek, T Adamowicz, D Gopalakrishnan, J Garcia, B Rini, P Grivas
Background: Advances in cancer genome sequencing have led to the development of various next-generation sequencing (NGS) platforms. There is paucity of data regarding concordance of different NGS tests carried out in the same patient. Methods: Here, we report a pilot analysis of 22 patients with metastatic urinary tract cancer and available NGS data from paired tumor tissue [FoundationOne (F1)] and cell-free circulating tumor DNA (ctDNA) [Guardant360 (G360)]. Results: The median time between the diagnosis of stage IV disease and the first genomic test was 23...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28945747/establishment-of-primary-mixed-cell-cultures-from-spontaneous-canine-mammary-tumors-characterization-of-classic-and-new-cancer-associated-molecules
#15
Luciana B Gentile, Marcia K Nagamine, Luiz R Biondi, Daniel S Sanches, Fábio Toyota, Tatiane M Giovani, Isis P de Jesus, Ivone I M da Fonseca, Nicolle Queiroz-Hazarbassanov, Bruno L Diaz, Cristina de O Massoco Salles Gomes, Maria Lucia Z Dagli
There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28938467/testis-determination-requires-a-specific-fgfr2-isoform-to-repress-foxl2
#16
Stefan Bagheri-Fam, Anthony D Bird, Liang Zhao, Janelle M Ryan, Meiyun Yong, Dagmar Wilhelm, Peter Koopman, Jacob V Eswarakumar, Vincent R Harley
Male sex determination in mammals relies on SRY-mediated up-regulation of SOX9 expression in XY gonads, whereas WNT/RSPO signalling and FOXL2 drive female sex determination in XX gonads. FGF9-signalling ensures sustained SOX9 expression through repression of one of the ovarian pathways (WNT signalling), while the significance of FGF-mediated repression of the FOXL2 pathway has not been studied. Previously, we demonstrated that FGFR2 is the receptor for FGF9 in the XY gonad. Whether a specific isoform (FGFR2b or FGFR2c) is required was puzzling...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28923346/role-of-fibroblast-growth-factor-receptors-fgfr-and-fgfr-like-1-fgfrl1-in-mesenchymal-stromal-cell-differentiation-to-osteoblasts-and-adipocytes
#17
T E Kähkönen, K K Ivaska, M Jian, K G Büki, H K Väänänen, P L Härkönen
Fibroblast growth factors (FGF) and their receptors (FGFRs) regulate many developmental processes including differentiation of mesenchymal stromal cells (MSC). We developed two MSC lines capable of differentiating to osteoblasts and adipocytes and studied the role of FGFRs in this process. We identified FGFR2 and fibroblast growth factor receptor like-1 (FGFRL1) as possible actors in MSC differentiation with gene microarray and qRT-PCR. FGFR2 and FGFRL1 mRNA expression strongly increased during MSC differentiation to osteoblasts...
September 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28919491/potential-involvement-of-fgf10-fgfr2-and-androgen-receptor-ar-in-renal-fibrosis-in-adult-male-rat-offspring-subjected-to-prenatal-exposure-to-di-n-butyl-phthalate-dbp
#18
Wen-Lan Sun, Yi-Ping Zhu, Xiu-Shi Ni, Da-Dao Jing, Yu-Ting Yao, Wei Ding, Zhi-Hong Liu, Guo-Xian Ding, Jun-Tao Jiang
BACKGROUND: We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) induces dysplasia of the kidney in newborn male offspring and renal fibrosis in adults. But the underlying mechanisms remain elusive. Fgf10/Fgfr2 and androgen receptor (AR) are known to be important for renal development. We therefore investigated whether these genes are involved in DBP-induced renal fibrosis. MATERIALS AND METHODS: Using Sprague-Dawley rats and rat renal proximal tubular cells (NRK52E), we determined the potential involvement of Fgf10, Fgfr2 and AR in DBP-induced renal fibrosis...
September 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28905937/somcl-085-a-novel-multi-targeted-fgfr-inhibitor-displays-potent-anticancer-activity-in-fgfr-addicted-human-cancer-models
#19
Xi-Fei Jiang, Yang Dai, Xia Peng, Yan-Yan Shen, Yi Su, Man-Man Wei, Wei-Ren Liu, Zhen-Bin Ding, Ao Zhang, Ying-Hong Shi, Jing Ai
Aberrant fibroblast growth factor receptor (FGFR) activation is found across a diverse spectrum of malignancies, especially those lacking effective treatments. SOMCL-085 is a novel FGFR-dominant multi-target kinase inhibitor. Here, we explored the FGFR-targeting anticancer activity of SOMCL-085 both in vitro and in vivo. Among a panel of 20 tyrosine kinases screened, SOMCL-085 potently inhibited FGFR1, FGFR2 and FGFR3 kinase activity, with IC50 values of 1.8, 1.9 and 6.9 nmol/L, respectively. This compound simultaneously inhibited the angiogenesis kinases VEGFR and PDGFR, but without obvious inhibitory effect on other 12 tyrosine kinases...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28901406/fgfr2-mutations-and-associated-clinical-observations-in-two-chinese-patients-with-crouzon-syndrome
#20
Ying Lin, Hongbin Gao, Siming Ai, Jacob V P Eswarakumar, Yi Zhu, Chuan Chen, Tao Li, Bingqian Liu, Hongye Jiang, Yuhua Liu, Yonghao Li, Qingxiu Wu, Haichun Li, Xiaoling Liang, Chenjin Jin, Xinhua Huang, Lin Lu
The aim of the present study was to identify mutations in the fibroblast growth factor receptor 2 (FGFR2) gene in patients with Crouzon syndrome and characterize the associated clinical features. A total of two Chinese patients diagnosed with Crouzon syndrome underwent complete examinations, including best‑corrected visual acuity, slit‑lamp, examination, fundus examination, optical coherence tomography and computed tomography of the skull. Genomic DNA was extracted from peripheral blood samples collected from the patients, as well as their family members and 200 unrelated control subjects from the same population...
November 2017: Molecular Medicine Reports
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