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fibroblast growth factor receptor

Stefan Z Lutz, Anita M Hennige, Andreas Peter, Marketa Kovarova, Charisis Totsikas, Jürgen Machann, Stefan M Kröber, Bianca Sperl, Erwin Schleicher, Fritz Schick, Martin Heni, Axel Ullrich, Hans-Ulrich Häring, Norbert Stefan
Context: The effect of a lifestyle intervention to reduce liver fat content in nonalcoholic fatty liver disease in humans is influenced by genetics. We hypothesized that the functionally active amino acid exchange in humans Gly388Arg (mouse homologue: Gly385Arg) in the fibroblast growth factor receptor 4 (FGFR4), which regulates bile acid, lipid and glucose metabolism, may determine the dynamics of hepatic lipid accumulation and insulin sensitivity in humans. Mechanisms of this substitution were studied in mice under normal chow and high-fat diet...
December 12, 2018: Journal of Clinical Endocrinology and Metabolism
Kazuya Koyama, Hisatsugu Goto, Shun Morizumi, Kozo Kagawa, Haruka Nishimura, Seidai Sato, Hiroshi Kawano, Yuko Toyoda, Hirohisa Ogawa, Sakae Homma, Yasuhiko Nishioka
The signaling pathways of growth factors including platelet-derived growth factor (PDGF) can be considered specific targets for overcoming the poor prognosis of idiopathic pulmonary fibrosis (IPF). Nintedanib, the recently approved multiple kinase inhibitor, has shown promising anti-fibrotic effects in IPF patients; however, its efficacy is still limited, and in some cases, treatment discontinuation is necessary due to toxicities such as gastrointestinal disorders. Therefore, more effective agents with less toxicity are still needed...
December 12, 2018: American Journal of Respiratory Cell and Molecular Biology
Karen E Wickersham, Theresa K Hodges, Martin J Edelman, Yang Song, Mintong Nan, Susan G Dorsey
BACKGROUND: Therapies targeting the epidermal growth factor receptor (EGFR) result in a painful rash, the most common and debilitating toxicity among patients with non-small cell lung cancer (NSCLC) who take EGFR tyrosine kinase inhibitor (TKI) therapy; however, predicting the development and the severity of the rash is difficult. OBJECTIVE: To examine how erlotinib-an EGFR TKI that NSCLC patients take to stop or slow tumor growth-altered the transcriptome of dermal fibroblasts...
December 12, 2018: Nursing Research
Leisl M Packer, Samantha J Stehbens, Vanessa F Bonazzi, Jennifer Gunter, Robert J Ju, Micheal Ward, Michael Gartside, Sara Byron, Pamela M Pollock
Endometrial cancer is the most commonly diagnosed gynaecological malignancy. Unfortunately, 15-20% of women demonstrate persistent or recurrent tumours that are refractory to current chemotherapies. We previously identified activating mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) in 12% (stage I/II) to 17% (stage III/IV) endometrioid ECs and found that these mutations are associated with shorter progression-free and cancer-specific survival. Although FGFR inhibitors are undergoing clinical trials for treatment of several cancer types, little is known about the mechanism by which they induce cell death...
December 8, 2018: Molecular Oncology
Elham Farhadi, Mahdi Mahmoudi, Farzaneh Rahmani, Bahman Yousefi, Abdolfattah Sarafnejad, Hoda Kavosi, Elham Karimizadeh, Ahmadreza Jamshidi, Farhad Gharibdoost
OBJECTIVES: Impaired wound healing and skin dehydration are the mainstay of systemic sclerosis (SSc) cutaneous manifestations. Aquaporin-3 (AQP3) has a pivotal role in skin hydration and wound healing. Epidermal growth factor receptor (EGFR) activation is impaired in SSc fibroblasts. It is unclear whether AQP3 downregulation or epidermal growth factor (EGF) signaling are the primary points of dysregulation in SSc patients. METHODS: Skin punch biopsies were obtained from 10 SSc patients and 10 healthy subjects...
December 7, 2018: Journal of Cellular Physiology
Long Zhou, Han-Yi Song, Lin-Lin Gao, Li-Yu Yang, Shuai Mu, Qin Fu
MicroRNAs (miRNAs/miRs) are post‑transcriptional regulators that serve important roles in osteoclastogenesis and bone metabolism; however, the roles of miRNAs have not been completely clarified. The present study aimed to investigate the effects of miR‑100‑5p on the mechanism of liver‑bone endocrine metabolism. A miRNA microarray analysis was conducted to evaluate the miRNA expression profile during receptor activator of nuclear factor‑κB ligand‑stimulated osteoclastogenesis. Hematoxylin and eosin and tartrate‑resistant acid phosphatase staining were performed to analyze the trabecular bone microstructure and osteoclast differentiation...
December 6, 2018: International Journal of Molecular Medicine
Maxime Vanmechelen, Diether Lambrechts, Thomas Van Brussel, Annelies Verbiest, Gabrielle Couchy, Patrick Schöffski, Herlinde Dumez, Philip R Debruyne, Evelyne Lerut, Jean-Pascal Machiels, Vincent Richard, Maarten Albersen, Vincent Verschaeve, Stéphane Oudard, Arnaud Méjean, Pascal Wolter, Jessica Zucman-Rossi, Benoit Beuselinck
BACKGROUND: There are no validated markers that predict response or resistance in patients with metastatic clear-cell renal cell carcinoma (mccRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors such as sunitinib and pazopanib. Recently, single nucleotide polymorphism (SNP) rs2981582 in Fibroblast Growth Factor Receptor 2 (FGFR2) was found to be associated with clinical outcome in patients with mccRCC treated with pazopanib and sunitinib. We aimed to validate these findings in patients treated with sunitinib...
November 16, 2018: Clinical Genitourinary Cancer
Nunthawan Nowwarote, Waleerat Sukarawan, Prasit Pavasant, Brian L Foster, Thanaphum Osathanon
BACKGROUND: Basic fibroblast growth factor (bFGF) regulates maintenance of stemness and modulation of osteo/odontogenic differentiation and mineralization in stem cells from human exfoliated deciduous teeth (SHEDs). Mineralization in the bones and teeth is in part controlled by pericellular levels of inorganic phosphate (Pi ), a component of hydroxyapatite, and inorganic pyrophosphate (PPi ), an inhibitor of mineralization. The progressive ankylosis protein (gene ANKH; protein ANKH) and ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1/ENPP1) increase PPi and inhibit mineralization, while tissue-nonspecific alkaline phosphatase (ALPL; TNAP) is a critical pro-mineralization enzyme that hydrolyzes PPi ...
December 10, 2018: Stem Cell Research & Therapy
Xinyi Wang, Jing Ai, Hongyan Liu, Xia Peng, Hui Chen, Yi Chen, Yi Su, Aijun Shen, Xun Huang, Jian Ding, Meiyu Geng
Acquired resistance severely hinders the application of small molecule inhibitors. Our understanding of acquired resistance related to fibroblast growth factor receptors (FGFRs) is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors and investigated the potential mechanisms underlying acquired resistance. We discovered that reprogramming of the secretome is closely associated with acquired resistance to FGFR inhibitors...
December 6, 2018: Molecular Cancer Therapeutics
Young-Chae Kim, Sangwon Byun, Sunmi Seok, Grace Guo, H Eric Xu, Byron Kemper, Jongsook Kim Kemper
BACKGROUND & AIMS: The nuclear receptor subfamily 0 group B member 2 (NR0B2, also called SHP) is expressed at high levels in liver and intestine. Postprandial fibroblast growth factor 19 (human FGF19, mouse FGF15) signaling increases the transcriptional activity of SHP. We studied the functions of SHP and FGF19 in intestines of mice, including their regulation of expression of the cholesterol transporter NPC1-like intracellular cholesterol transporter 1 (NPC1L1) and cholesterol absorption...
December 3, 2018: Gastroenterology
Dongyang Wang, Jianjun Zhang, Zengjun Li, Jianjun Han, Yongsheng Gao, Ming Chen, Yanqing Li
Fibroblast growth factor 19 (FGF19) promotes tumor growth in various types of cancer, but its function has not been investigated in the context of colorectal adenoma. Here, we report that FGF19 expression was greater in colorectal adenoma than in normal tissues, as measured by an enzyme-linked immunosorbent assay, quantitative reverse-transcription PCR and immunohistochemistry. FGF19 expression was also elevated in a subset of human colon cancer cell lines. Moreover, FGF receptor 4 (FGFR4), the cognate receptor for FGF19, was upregulated in colorectal adenoma tissues...
December 5, 2018: Digestive Diseases
Abha Sahni, Hema P Narra, Jignesh Patel, Sanjeev K Sahni
Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate⁻early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R...
December 1, 2018: Cells
Ming Chang Hu, Mingjun Shi, Orson W Moe
Alpha-Klotho is a member of the Klotho family consisting of two other single-pass transmembrane proteins: βKlotho and γKlotho; αKlotho has been shown to circulate in the blood. Fibroblast growth factor (FGF)23 is a member of the FGF superfamily of 22 genes/proteins. αKlotho serves as a co-receptor with FGF receptors (FGFRs) to provide a receptacle for physiological FGF23 signaling including regulation of phosphate metabolism. The extracellular domain of transmembrane αKlotho is shed by secretases and released into blood circulation (soluble αKlotho)...
December 1, 2018: Pflügers Archiv: European Journal of Physiology
R Fellin, E Manzato
AIMS: To review the formation, catabolism, and the possible atherogenic properties of Lp-X. DATA SYNTHESIS: The conversion of cholesterol to bile acids is regulated by several mechanisms including cholesterol 7 alpha hydroxylase, fibroblast growth factor 19, and farnesoid X receptors. During cholestasis these mechanisms are altered and there is an accumulation of bile acids and cholesterol in plasma. The hypercholesterolemia observed in cholestasis is due to the presence of an anomalous lipoprotein called lipoprotein-X (Lp-X)...
September 26, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Kosuke Yamaguchi, Haruka Sudo, Kazushi Imai
An increase in the vasculature is one of most representative changes in the synovial tissue of joints in rheumatoid arthritis (RA) and is closely associated with disease progression. Although the vasculatures are believed to be a result of VE-cadherin-dependent angiogenesis and a possible therapeutic target of the disease, synovial fibroblastic cells express VE-cadherin and form tube-like structures, suggesting that vasculatures in RA synovium may not simply result from angiogenesis. This paper analyzes a mechanism of VE-cadherin expression by rheumatoid arthritic synovial fibroblast-like cells (RSFLs) and their involvement in the tube-like formation...
November 28, 2018: Biochemical and Biophysical Research Communications
Mariko Kawai, David Herrmann, Alisa Fuchs, Shuofei Cheng, Anna Ferrer-Vaquer, Rebekka Götz, Katrin Driller, Annette Neubüser, Kiyoshi Ohura
Most facial bones, including frontal bones, are derived from neural crest cells through intramembranous ossification. Fibroblast growth factor receptor 1 (Fgfr1) plays a pivotal role in craniofacial bone development, and loss of Fgfr1 leads to cleft palate and facial cleft defects in newborn mice. However, the potential role of the Fgfr1 gene in neural crest cell-mediated craniofacial development remains unclear. To investigate the role of Fgfr1 in neural crest cells, we analyzed Wnt1-Cre;Fgfr1flox/flox mice...
November 29, 2018: Medical Molecular Morphology
Tobias Feldreich, Christoph Nowak, Tove Fall, Axel C Carlsson, Juan-Jesus Carrero, Jonas Ripsweden, Abdul Rashid Qureshi, Olof Heimbürger, Peter Barany, Peter Stenvinkel, Nicolas Vuilleumier, Philip A Kalra, Darren Green, Johan Ärnlöv
INTRODUCTION: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]...
November 29, 2018: Journal of Nephrology
Jen-Kit Tan, Faizul Jaafar, Suzana Makpol
BACKGROUND: Replicative senescence of human diploid fibroblasts (HDFs) has been used as a model to study mechanisms of cellular aging. Gamma-tocotrienol (γT3) is one of the members of vitamin E family which has been shown to increase proliferation of senescent HDFs. However, the modulation of protein expressions by γT3 in senescent HDFs remains to be elucidated. Therefore, this study aimed to determine the differentially expressed proteins (DEPs) in young and senescent HDFs; and in vehicle- and γT3-treated senescent HDFs using label-free quantitative proteomics...
November 29, 2018: BMC Complementary and Alternative Medicine
Jin Wu, Xuran Chu, Chengshui Chen, Saverio Bellusci
During organogenesis and pathogenesis, fibroblast growth factor 10 (Fgf10) regulates mesenchymal cell differentiation in the lung. Different cell types reside in the developing lung mesenchyme. Lineage tracing in vivo was used to characterize these cells during development and disease. Fgf10-positive cells in the early lung mesenchyme differentiate into multiple lineages including smooth muscle cells (SMCs), lipofibroblasts (LIFs) as well as other cells, which still remain to be characterized. Fgf10 signaling has been reported to act both in an autocrine and paracrine fashion...
2018: Frontiers in Genetics
Zhuo Chen, Lin-Jiang Tong, Bai-You Tang, Hong-Yan Liu, Xin Wang, Tao Zhang, Xian-Wen Cao, Yi Chen, Hong-Lin Li, Xu-Hong Qian, Yu-Fang Xu, Hua Xie, Jian Ding
The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor with an IC50 of 19 nM among a panel of 20 tyrosine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway...
November 28, 2018: Acta Pharmacologica Sinica
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