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https://www.readbyqxmd.com/read/29137286/fibroblast-growth-factor-modulates-mast-cell-recruitment-in-a-murine-model-of-prostate-cancer
#1
Roberto Ronca, Roberto Tamma, Daniela Coltrini, Simona Ruggieri, Marco Presta, Domenico Ribatti
Mast cells are important modifiers of prostate tumor microenvironment. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) system plays a non-redundant autocrine/paracrine role in the growth, vascularization and progression of prostate tumors. Accordingly, the FGF antagonist long pentraxin-3 (PTX3) and the PTX3-derived small molecule FGF-trap NSC12 have been shown to inhibit the growth and vascularization of different FGF-dependent tumor types, including prostate cancer. In this study, we show that recombinant FGF2 is able to cause mast cell recruitment in vivo in the Matrigel plug assay...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29122742/myotube-migration-to-cover-and-shape-the-testis-of-drosophila-depends-on-heartless-cadherin-catenin-and-myosin-ii
#2
Silke Rothenbusch-Fender, Katharina Fritzen, Maik C Bischoff, Detlev Buttgereit, Susanne F Oenel, Renate Renkawitz-Pohl
During Drosophila metamorphosis, nascent testis myotubes migrate from the prospective seminal vesicle of the genital disc onto pupal testes and then further to cover the testes with multinucleated smooth-like muscles. Here we show that DWnt2 is likely required for determination of testis-relevant myoblasts on the genital disc. Knock down of FGFR Heartless by RNAi and a dominant-negative version revealed multiple functions of Heartless, namely regulation of the amount of myoblasts on the genital disc, connection of seminal vesicles and testes, and migration of muscles along the testes...
November 9, 2017: Biology Open
https://www.readbyqxmd.com/read/29101463/a-drug-drug-interaction-study-to-assess-the-effect-of-the-cyp1a2-inhibitor-fluvoxamine-on-the-pharmacokinetics-of-dovitinib-tki258-in-patients-with-advanced-solid-tumors
#3
Vincent A de Weger, Sanjay Goel, Roger von Moos, Jan H M Schellens, Nicholas Mach, Eugene Tan, Suraj Anand, Jeffrey W Scott, Ulrik Lassen
PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS: Non-smoking patients of ≥ 18 years with advanced solid tumors, excluding breast cancer, were included. Patients were treated with a dose of 300 mg in 5 days on/2 days off schedule...
November 3, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29097598/fgf-fgfr-mediates-the-activity-dependent-dendritogenesis-of-layer-iv-neurons-during-barrel-formation
#4
Jui-Yen Huang, Marisha Lynn Miskus, Hui-Chen Lu
Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) are known for their potent effects on cell proliferation/differentiation and cortical patterning in the developing brain. However, little is known regarding FGFs/FGFRs' roles in cortical circuit formation. Here we show that Fgfr1/2/3 and Fgf7/9/10/22 mRNAs are expressed in the developing primary somatosensory (S1) barrel cortex. Barrel cortex layer IV spiny stellate cells (bSCs) are the primary recipients of ascending sensory information via thalamocortical axons (TCAs)...
November 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29094504/a-link-between-the-fibroblast-growth-factor-axis-and-the-mir-16-family-reveals-potential-new-treatment-combinations-in-mesothelioma
#5
Karin Schelch, Michaela B Kirschner, Marissa Williams, Yuen Yee Cheng, Nico van Zandwijk, Michael Grusch, Glen Reid
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with very limited therapeutic options. Fibroblast growth factor (FGF) signals play important roles in mesothelioma cell growth. Several FGFs and FGF receptors (FGFRs) are predicted targets of the miR-15/16 family, which is downregulated in MPM. The aim of this study was to explore the link between the miR-15/16 family and the FGF-axis in MPM. Expression analyses via RT-qPCR showed downregulation of the FGF-axis after transfection with miR-15/16 mimics...
November 1, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29094049/diagnostic-predictive-prognostic-and-therapeutic-molecular-biomarkers-in-third-millennium-a-breakthrough-in-gastric-cancer
#6
REVIEW
Nicola Carlomagno, Paola Incollingo, Vincenzo Tammaro, Gaia Peluso, Niccolò Rupealta, Gaetano Chiacchio, Maria Laura Sandoval Sotelo, Gianluca Minieri, Antonio Pisani, Eleonora Riccio, Massimo Sabbatini, Umberto Marcello Bracale, Armando Calogero, Concetta Anna Dodaro, Michele Santangelo
Introduction: Gastric cancer is the fifth most common cancer and the third cause of cancer death. The clinical outcomes of the patients are still not encouraging with a low rate of 5 years' survival. Often the disease is diagnosed at advanced stages and this obviously negatively affects patients outcomes. A deep understanding of molecular basis of gastric cancer can lead to the identification of diagnostic, predictive, prognostic, and therapeutic biomarkers. Main Body: This paper aims to give a global view on the molecular classification and mechanisms involved in the development of the tumour and on the biomarkers for gastric cancer...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29093661/syndromic-craniosynostosis-can-define-new-candidate-genes-for-suture-development-or-result-from-the-non-specifc-effects-of-pleiotropic-genes-rasopathies-and-chromatinopathies-as-examples
#7
REVIEW
Marcella Zollino, Serena Lattante, Daniela Orteschi, Silvia Frangella, Paolo N Doronzio, Ilaria Contaldo, Eugenio Mercuri, Giuseppe Marangi
Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15-30% of cases craniosynostosis occurs in association with other physical anomalies and it is referred to as syndromic craniosynostosis. Syndromic forms of craniosynostosis arise from mutations in genes belonging to the Fibroblast Growth Factor Receptor (FGFR) family and the interconnected molecular pathways in most cases...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29071223/an-alignment-independent-3d-qsar-study-of-fgfr2-tyrosine-kinase-inhibitors
#8
Behzad Jafari, Maryam Hamzeh-Mivehroud, Ali Akbar Alizadeh, Mehdi Sharifi, Siavoush Dastmalchi
Purpose: Receptor tyrosine kinase (RTK) inhibitors are widely used pharmaceuticals in cancer therapy. Fibroblast growth factor receptors (FGFRs) are members of RTK superfamily which are highly expressed on the surface of carcinoma associate fibroblasts (CAFs). The involvement of FGFRs in different types of cancer makes them promising target in cancer therapy and hence, the identification of novel FGFR inhibitors is of great interest. In the current study we aimed to develop an alignment independent three dimensional quantitative structure-activity relationship (3D-QSAR) model for a set of 26 FGFR2 kinase inhibitors allowing the prediction of activity and identification of important structural features for these inhibitors...
September 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29068468/expression-of-the-fgfr2c-mesenchymal-splicing-variant-in-human-keratinocytes-inhibits-differentiation-and-promotes-invasion
#9
Danilo Ranieri, Benedetta Rosato, Monica Nanni, Francesca Belleudi, Maria Rosaria Torrisi
The altered isoform switching of the fibroblast growth factor receptor 2 (FGFR2) and aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells is involved in cancer progression. We have recently described that the ectopic expression of FGFR2c in normal human keratinocytes induces epithelial-mesenchymal transition and leads to invasiveness and anchorage-independent growth. Here we extended our analysis to the effects of this FGFR2c forced expression on human keratinocyte differentiation and stratification...
October 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29067649/interplay-between-tgf-%C3%AE-signaling-and-receptor-tyrosine-kinases-in-tumor-development
#10
REVIEW
Qiaoni Shi, Ye-Guang Chen
Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors...
October 23, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29061644/comprehensive-pharmacogenomic-profiling-of-malignant-pleural-mesothelioma-identifies-a-subgroup-sensitive-to-fgfr-inhibition
#11
Josine M Quispel-Janssen, Jitendra Badhai, Laurel Schunselaar, Stacey Price, Jonathan S Brammeld, Francesco Iorio, Krishna K Kolluri, Mathew J Garnett, Anton Berns, Paul Baas, Ultan McDermott, Jacques Neefjes, Constantine Alifrangis
PURPOSE: Despite intense research, treatment options for patients with mesothelioma are limited and offer only modest survival advantage. We screened a large panel of compounds in multiple mesothelioma models, and correlated sensitivity with a range of molecular features to detect biomarkers of drug response. EXPERIMENTAL DESIGN: We utilised a high-throughput chemical inhibitor screen in a panel of 889 cancer cell lines, including both immortalised and primary early passage mesothelioma lines, alongside comprehensive molecular characterisation using Illumina whole exome sequencing, copy number analysis and Affymetrix array whole transcriptome profiling...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29055704/comparative-study-of-the-effect-of-different-fucoidans-from-sargassum-maclurei-and-saccharina-japonica-on-fgfs-fgfr-signaling-activation-in-baf3-cells
#12
Lihua Geng, Ningning Hou, Meng Zhang, Yingjie Xu, Qi Zhang, Jing Wang, Lijuan Zhang, Quanbin Zhang
Different sulfated polysaccharides have distinct abilities to activate specific fibroblast growth factor (FGF) signaling pathways in FGFR1c-expressing BaF3 cells. In the current study, we first isolated and characterized different fucoidan fractions from Sargassum maclurei and Saccharina japonica. All of the fucoidan fractions were incubated with BaF3 cells in the presence of FGF-1, -2, -7, -8, -9, and -10, respectively, to evaluate their FGFs/FGFR1c signal-activating ability. Our data showed that low molecular weight fucoidan fraction from S...
October 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29048661/combination-of-fgfr4-inhibitor-blu9931-and-5-fluorouracil-effects-on-the-biological-characteristics-of-colorectal-cancer-cells
#13
Dongbao Jiang, Jingjing Li, Jie Li, Min Wang, Chao Han, Xinru Wang, Chunlin Zhao, Yanwei Ye
The aim of this study was to explore the effects of single agent treatments and combination of Blu9931 and 5-fluorouracil (5-FU) on the biological characteristics of colorectal cancer cells and its mechanism. Blu9931 is the first selective small molecule inhibitor of the fibroblast growth factor receptor 4 (FGFR4) and exquisitely selective for FGFR4 versus other FGFR family members and all other kinases. The colorectal cancer cells HCT116 and SW620 with high expression of FGFR4 were selected for a series of functional tests including cell viability, cell proliferation, apoptosis and cell cycle detection...
October 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29042943/suxiao-jiuxin-pill-protects-cardiomyocytes-against-mitochondrial-injury-and-alters-gene-expression-during-ischemic-injury
#14
Xiaofen Ruan, Tiejun Chen, Xiaolong Wang, Yiping Li
Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29040558/constitutively-active-fgfr3-disrupts-primary-cilium-length-and-ift20-trafficking-in-various-chondrocyte-models-of-achondroplasia
#15
Ludovic Martin, Nabil Kaci, Valentin Estibals, Nicolas Goudin, Meriem Garfa-Traore, Catherine Benoist-Lasselin, Emilie Dambroise, Laurence Legeai-Mallet
FGFR3 (fibroblast growth factor receptor 3) gain-of-function mutations cause dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The constitutive activation of FGFR3 disrupts the normal process of skeletal growth. Bone-growth anomalies have been identified in skeletal ciliopathies, in which primary cilia (PC) function is disrupted. In human ACH and TD, the impact of FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the constitutively-active FGFR3 perturbed PC length and the sorting and trafficking of IFT20 to the PC...
October 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29030113/proteomic-analyses-of-signalling-complexes-associated-with-receptor-tyrosine-kinase-identify-novel-members-of-fibroblast-growth-factor-receptor-3-interactome
#16
Lukas Balek, Pavel Nemec, Peter Konik, Michaela Kunova Bosakova, Miroslav Varecha, Iva Gudernova, Jirina Medalova, Deborah Krakow, Pavel Krejci
Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3)...
October 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29021995/tumor-induced-osteomalacia
#17
Pablo Florenzano, Rachel I Gafni, Michael T Collins
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23) that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/29019756/imaging-of-skeletal-disorders-caused-by-fibroblast-growth-factor-receptor-gene-mutations
#18
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/29017058/androgen-receptor-pathway-independent-prostate-cancer-is-sustained-through-fgf-signaling
#19
Eric G Bluemn, Ilsa M Coleman, Jared M Lucas, Roger T Coleman, Susana Hernandez-Lopez, Robin Tharakan, Daniella Bianchi-Frias, Ruth F Dumpit, Arja Kaipainen, Alexandra N Corella, Yu Chi Yang, Michael D Nyquist, Elahe Mostaghel, Andrew C Hsieh, Xiaotun Zhang, Eva Corey, Lisha G Brown, Holly M Nguyen, Kenneth Pienta, Michael Ittmann, Michael Schweizer, Lawrence D True, David Wise, Paul S Rennie, Robert L Vessella, Colm Morrissey, Peter S Nelson
Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These "double-negative" PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29017052/cellular-origin-of-androgen-receptor-pathway-independent-prostate-cancer-and-implications-for-therapy
#20
W Nathaniel Brennen, John T Isaacs
In this issue of Cancer Cell, Bluemn et al. report that ∼20% of metastatic castration-resistant prostate cancers express neither AR nor neuroendocrine genes and show AR pathway-independent growth, driven instead by a FGFR/MAPK/ID1 signaling cascade. These results provide a strong rationale for co-targeting AR bypass pathways with initial AR antagonism.
October 9, 2017: Cancer Cell
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