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https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#1
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29775937/design-synthesis-and-biological-evaluation-of-a-series-of-novel-2-benzamide-4-6-oxy-n-methyl-1-naphthamide-pyridine-derivatives-as-potent-fibroblast-growth-factor-receptor-fgfr-inhibitors
#2
Manman Wei, Xia Peng, Li Xing, Yang Dai, Ruimin Huang, Meiyu Geng, Ao Zhang, Jing Ai, Zilan Song
Starting from the phase II clinical FGFR inhibitor lucitanib (2), we conducted a medicinal chemistry approach by opening the central quinoline skeleton coupled with a scaffold hopping process thus leading to a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives. Compound 25a was identified to show selective and equally high potency against FGFR1/2 and VEGFR2 with IC50 values less than 5.0 nM. Significant antiproliferative effects on both FGFR1/2 and VEGFR2 aberrant cancer cells were observed...
May 15, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29771000/molecular-testing-in-holoprosencephaly
#3
Paul Kruszka, Ariel F Martinez, Maximilian Muenke
Holoprosencephaly (HPE) is a structural brain anomaly characterized by failure of the forebrain to separate during early embryogenesis. Both genetic and environmental etiologies of HPE have been discovered over the last three decades. Traditionally, the genetic workup for HPE has been a karyotype, chromosomal microarray, and/or Sanger sequencing of select genes. The recent increased availability of next-generation sequencing has changed the molecular diagnostic landscape for HPE, associating new genes with this disorder such as FGFR1...
May 17, 2018: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/29767670/treatment-of-the-myeloid-lymphoid-neoplasm-with-fgfr1-rearrangement-with-fgfr1-inhibitor
#4
S Verstovsek, V Subbiah, L Masarova, C C Yin, G Tang, T Manshouri, E Asatiani, N G Daver
No abstract text is available yet for this article.
May 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29764586/-relationship-between-fgfr1-gene-regulation-of-circulating-tumor-cells-and-clinical-features-of-non-small-cell-lung-cancer
#5
Lei Liu, Cheng Huang, Li Li, Naixin Liang, Shanqing Li
BACKGROUND: The methods of detection for recurrence and metastasis in patients with non-small cell lung cancer (NSCLC) have hysteresis and one-sidedness. This study summarizes the relationship between the circulating tumor cell (CTC) in peripheral blood, expression of fibroblast growth factor receptor 1 (FGFR1) and clinic pathological features in 30 patients with NSCLC so as to provide new ideas for the detection of tumor recurrence and metastasis. METHODS: To analyze the clinical data and CTC detection data of 30 cases of NSCLC in Department of Thoracic Surgery, Peking Union Medical College Hospital from November 2016 to June 2017...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29761369/oligodendrogliomas-in-pediatric-and-teenage-patients-only-rarely-exhibit-molecular-markers-and-patients-have-excellent-survivals
#6
Yan-Xi Li, Abudumijiti Aibaidula, Zhifeng Shi, Hong Chen, Kay Ka-Wai Li, Nellie Yuk-Fei Chung, Ryan Rui Yang, Danny Tat-Ming Chan, Wai Sang Poon, Ka Lok Ryan Lee, Ying Mao, Jinsong Wu, Aden Ka-Yin Chan, Liangfu Zhou, Ho-Keung Ng
Although oligodendrogliomas appear histologically similar in adult and pediatric patients, the latter have only been rarely studied and most of those studies did not have long follow-up. We examined 55 oligodendroglial tumors from pediatric and teenage patients for their biomarkers with formalin-fixed paraffin-embedded tissues and studied their survival status. None of the tumors harbored 1p/19q codeletion or IDH mutation. Mutations in TERTp (4%), BRAF (11%), FGFR1 (3%) and H3F3A (5%), fusions of BRAF (8%) and FGFR1 (8%) were found sparingly and almost all in a mutually exclusive manner...
May 14, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29754994/corrigendum-to-the-hippo-yap1-pathway-interacts-with-fgfr1-signaling-to-maintain-stemness-in-lung-cancer-canc-lett-423-2018-36-46
#7
Tingting Lu, Ziming Li, Ying Yang, Wenxiang Ji, Yongfeng Yu, Xiaomin Niu, Qingyu Zeng, Weiliang Xia, Shun Lu
No abstract text is available yet for this article.
May 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29750313/cross-link-regulation-of-precursor-n-cadherin-and-fgfr1-by-gdnf-increases-u251mg-cell-viability
#8
Chuan-Xi Tang, Yan-Xia Gu, Xin-Feng Liu, Shu-Yan Tong, Abiola A Ayanlaja, Yue Gao, Guang-Quan Ji, Ye Xiong, Lin-Yan Huang, Dian-Shuai Gao
Glial cell line-derived neurotrophic factor (GDNF) is considered to be involved in the development of glioma. However, uncovering the underlying mechanism of the proliferation of glioma cells is a challenging work in progress. We have identified the binding of the precursor of N-cadherin (proN-cadherin) and GDNF on the cell membrane in previous studies. In the present study, we observed increased U251 Malignant glioma (U251MG) cell viability by exogenous GDNF (50 ng/ml). We also confirmed that the high expression of the proN-cadherin was stimulated by exogenous GDNF...
April 30, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29748524/high-affinity-promotes-internalization-of-engineered-antibodies-targeting-fgfr1
#9
Łukasz Opaliński, Jakub Szymczyk, Martyna Szczepara, Marika Kucińska, Daniel Krowarsch, Małgorzata Zakrzewska, Jacek Otlewski
Fibroblast growth factor receptor 1 (FGFR1) is a plasma membrane protein that transmits signals from the extracellular environment, regulating cell homeostasis and function. Dysregulation of FGFR1 leads to the development of human cancers and noncancerous diseases. Numerous tumors overproduce FGFR1, making this receptor a perspective target for cancer therapies. Antibody-drug conjugates (ADCs) are highly potent and selective anticancer agents. ADCs are composed of antibodies (targeting factors) fused to highly cytotoxic drugs (warheads)...
May 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29748005/genomic-alterations-of-plasma-cell-free-dnas-in-small-cell-lung-cancer-and-their-clinical-relevance
#10
Meijun Du, Jonathan Thompson, Hannah Fisher, Peng Zhang, Chiang-Ching Huang, Liang Wang
OBJECTIVES: To identify genomic variations in cell-free DNA (cfDNA) and evaluate their clinical utility in small cell lung cancer (SCLC). MATERIALS AND METHODS: We performed whole genome sequencing using plasma cfDNAs derived from 24 SCLC patients for copy number variation (CNV) analysis, and targeted sequencing using 17 pairs of plasma cfDNA and their matched gDNA for mutation analysis. We defined somatic mutations by comparing cfDNA to its matched gDNA with 5% variant alleles as the cutoff for mutation calls...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29743589/dual-inhibition-of-bcl-xl-and-mcl-1-is-required-to-induce-tumour-regression-in-lung-squamous-cell-carcinomas-sensitive-to-fgfr-inhibition
#11
Clare E Weeden, Casey Ah-Cann, Aliaksei Z Holik, Julie Pasquet, Jean-Marc Garnier, Delphine Merino, Guillaume Lessene, Marie-Liesse Asselin-Labat
Genetic alterations in the fibroblast growth factor receptors (FGFRs) have been described in multiple solid tumours including bladder cancer, head and neck and lung squamous cell carcinoma (SqCC). However, recent clinical trials showed limited efficacy of FGFR-targeted therapy in lung SqCC, suggesting combination therapy may be necessary to improve patient outcomes. Here we demonstrate that FGFR therapy primes SqCC for cell death by increasing the expression of the pro-apoptotic protein BIM. We therefore hypothesised that combining BH3-mimetics, potent inhibitors of pro-survival proteins, with FGFR-targeted therapy may enhance the killing of SqCC cells...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29735550/microrna-339-promotes-development-of-stem-cell-leukemia-lymphoma-syndrome-via-downregulation-of-the-bcl2l11-and-bax-pro-apoptotic-genes
#12
Tianxiang Hu, Yating Chong, Sumin Lu, Rebecca Wang, Haiyan Qin, Jeane Silva, Eiko Kitamura, Chang-Sheng Chang, LesleyAnn Hawthorn, John K Cowell
Development of myeloid and lymphoid neoplasms related to overexpression of FGFR1 kinases as a result of chromosome translocations depends on promotion of a stem cell phenotype, suppression of terminal differentiation, and resistance to apoptosis. These phenotypes are related to the stem cell leukemia/lymphoma syndrome (SCLL), which arises through the effects of activated FGFR1 kinase on gene transcription, including dysregulation of microRNAs. In a screen for miRNAs that are directly regulated by FGFR1 and that stimulate cell proliferation and survival, we identified miR-339-5p, which is highly upregulated in cells carrying various different chimeric kinases...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29734851/design-synthesis-and-biological-evaluation-of-4-bromo-n-3-5-dimethoxyphenyl-benzamide-derivatives-as-novel-fgfr1-inhibitors-for-treatment-of-non-small-cell-lung-cancer
#13
Zixin Xie, Donghua Cheng, Lu Luo, Guoliang Shen, Suwei Pan, Yaqian Pan, Bo Chen, Xuebao Wang, Zhiguo Liu, Yuan Zhang, Faqing Ye
A series of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives were designed and synthesised as novel fibroblast growth factor receptor-1 (FGFR1) inhibitors. We found that one of the most promising compounds, C9, inhibited five non-small cell lung cancer (NSCLC) cell lines with FGFR1 amplification, including NCI-H520, NCI-H1581, NCI-H226, NCI-H460 and NCI-H1703. Moreover, the IC50 values for the compound C9 were 1.36 ± 0.27 µM, 1.25 ± 0. 23 µM, 2.31 ± 0.41 µM, 2.14 ± 0.36 µM and 1...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29733511/lenvatinib-inhibits-angiogenesis-and-tumor-fibroblast-growth-factor-signaling-pathways-in-human-hepatocellular-carcinoma-models
#14
Masahiro Matsuki, Taisuke Hoshi, Yuji Yamamoto, Megumi Ikemori-Kawada, Yukinori Minoshima, Yasuhiro Funahashi, Junji Matsui
Unresectable hepatocellular carcinoma (uHCC) is one of the most lethal and prevalent cancers worldwide, and current systemic therapeutic options for uHCC are limited. Lenvatinib, a multiple receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), recently demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority to sorafenib in a phase 3 study of uHCC. Here, we investigated mechanisms underlying the antitumor activity of lenvatinib in preclinical HCC models...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29728520/-fgfr1-actionable-mutations-molecular-specificities-and-outcome-of-adult-midline-gliomas
#15
Alberto Picca, Giulia Berzero, Franck Bielle, Mehdi Touat, Julien Savatovsky, Marc Polivka, Elena Trisolini, Sheida Meunier, Yohann Schmitt, Ahmed Idbaih, Khe Hoang-Xuan, Jean-Yves Delattre, Karima Mokhtari, Anna Luisa Di Stefano, Marc Sanson
OBJECTIVE: To characterize the prevalence and prognostic significance of major driver molecular alterations in adult midline diffuse gliomas (MLG). METHODS: Adults with histologically proven MLG diagnosed between 1996 and 2017 were identified from our tumor bank, systematically reviewed, and reclassified according to WHO 2016. Targeted sequencing was performed, including determination of H3F3A , HIST1H3B , TERTp , IDH1/2 , FGFR1 , p16/CDKN2A , and EGFR status. RESULTS: A total of 116 adult patients (M/F 71/45, median age 46...
May 4, 2018: Neurology
https://www.readbyqxmd.com/read/29726090/gene-expression-signatures-prognostic-for-relapse-in-stage-i-testicular-germ-cell-tumors-tgct
#16
Jeremy Lewin, Laleh Soltan Ghoraie, Philippe L Bedard, Robert J Hamilton, Peter Chung, Malcolm Moore, Michael A S Jewett, Lynn Anson-Cartwright, Carl Virtanen, Neil Winegarden, Julie Tsao, Padraig Warde, Joan Sweet, Benjamin Haibe-Kains, Aaron R Hansen
OBJECTIVES: To identify differentially expressed genes between relapsed (R) and non-relapsed (NR) clinical stage I (CSI) testicular germ cell tumor (TGCT). MATERIALS AND METHODS: We reviewed patients with CSI non-seminoma(NS) and seminoma(S) from an institutional database (2000-2012) managed by active surveillance. NR-NS and NR-S patients were defined as being relapse free after 2 and 3 years of surveillance respectively. RNA extraction and gene expression analysis was performed on archival primary tumor samples and Gene-Set-Enrichment-Analysis (GSEA) was conducted in order to identify differentiating biological pathways...
May 3, 2018: BJU International
https://www.readbyqxmd.com/read/29722558/is-fibroblast-growth-factor-signaling-pathway-a-victim-of-receptor-tyrosine-kinase-inhibition-in-pulmonary-parenchymal-and-vascular-remodeling
#17
Elie El Agha, Felix Schwind, Clemens Ruppert, Andreas Günther, Saverio Bellusci, Ralph Theo Schermuly, Djuro Kosanovic
Idiopathic pulmonary arterial hypertension (IPAH), pulmonary hypertension (PH) due to lung disease and/or hypoxia and idiopathic pulmonary fibrosis (IPF) are increasingly recognized as important contributors to mortality and morbidity worldwide. Among others, the current treatment paradigm considers broad inhibition of receptor tyrosine kinases, a strategy that likely leads to collateral inhibition of signaling pathways that are critical for lung repair and regeneration. Fibroblast growth factor 7 (FGF7) and FGF10 signaling in the lung through FGF receptor 2 (FGFR2) are involved in epithelial cell protection and renewal, and mutations in their corresponding genes in humans are linked to increased susceptibility to lung pathologies such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29720732/fgfr1-fusion-kinase-regulation-of-myc-expression-drives-development-of-stem-cell-leukemia-lymphoma-syndrome
#18
Tianxiang Hu, Qing Wu, Yating Chong, Haiyan Qin, Candace J Poole, Jan van Riggelen, Mingqiang Ren, John K Cowell
Oncogenic transformation of hematopoietic stem cells by chimeric fusion kinases causing constitutive activation of FGFR1 leads to a stem cell leukemia/lymphoma (SCLL) syndrome, accompanied by widespread dysregulation of gene activity. We now show that FGFR1 activation is associated with upregulation of MYC and pharmacological suppression of FGFR1 activation leads to downregulation of MYC and suppression of MYC target genes. Luciferase reporter assays demonstrate that FGFR1 can directly regulate MYC expression and this effect is enhanced in the presence of chimeric FGFR1 kinases...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29720668/central-role-of-the-proximal-tubular-%C3%AE-klotho-fgf-receptor-complex-in-fgf23-regulated-phosphate-and-vitamin-d-metabolism
#19
Ai Takeshita, Kazuki Kawakami, Kenryo Furushima, Masayasu Miyajima, Kazushige Sakaguchi
Fibroblast growth factor 23 (FGF23) plays critical roles in phosphate handling and vitamin D metabolism in the kidney. However, the effector cells of FGF23 in the kidney remain unclear. αKlotho, a putative enzyme possessing β-glucuronidase activity and also a permissive co-receptor for FGF23 to bind to FGF receptors (FGFRs), is expressed most abundantly in distal convoluted tubules, whereas it is expressed modestly in proximal tubules. Key molecular players of phosphate homeostasis and vitamin D-metabolizing enzymes are known to localize in proximal tubules...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29715147/relationship-and-predictive-role-of-the-dual-expression-of-fgfr-and-il-8-in-metastatic-renal-cell-carcinoma-treated-with-targeted-agents
#20
Roberto Iacovelli, Michele DE Tursi, Claudia Mosillo, Antonio Ciardi, Consiglia Carella, Clara Natoli, Giuseppe Naso, Enrico Cortesi
BACKGROUND/AIM: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients. MATERIALS AND METHODS: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry. RESULTS: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively...
May 2018: Anticancer Research
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