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fibroblast growth factor receptor

Masoud Najafi, Bagher Farhood, Keywan Mortezaee
Regulatory T cells (Tregs) represent a low number of T-cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross-talks with other immunosuppressive cells including cancer-associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid-derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells...
October 14, 2018: Journal of Cellular Physiology
Wu Luo, Xiao-Mian Lin, Tian-Xiang Wang, Jia-Long Cai, Xiang-Feng Zeng, Cai-Rong Zhu, Rong-Zhen Li, Heng Wang, Xiao-Ping Wu
Previous studies suggest that specific binding to the complex consisting of fibroblast growth factor receptor-1 (FGFR1) and the coreceptor beta-Klotho (KLB) is the premise for human FGF19 and FGF21 activating the downstream signaling cascades, and regulating the metabolic homeostasis. However, it was found that human FGF21 loses its ability to bind to FGFR1-KLB after iodination with Na125 I and chloramine T, whereas human FGF19 retained its affinity for FGFR1-KLB even after iodination. The molecular mechanisms underlying these differences remained elusive...
October 14, 2018: Journal of Cellular Physiology
Manoj K Gupta, Dario F De Jesus, Sevim Kahraman, Ivan A Valdez, Farnaz Shamsi, Lian Yi, Adam C Swensen, Yu-Hua Tseng, Wei-Jun Qian, Rohit N Kulkarni
OBJECTIVES: Insulin receptor (IR)-mediated signaling is involved in the regulation of pluripotent stem cells; however, its direct effects on regulating the maintenance of pluripotency and lineage development are not fully understood. The main objective of this study is to understand the role of IR signaling in pluripotency and lineage development. METHODS: To explore the role of IR signaling, we generated IR knock-out (IRKO) mouse induced pluripotent stem cells (miPSCs) from E14...
September 19, 2018: Molecular Metabolism
Jana Kleiner, Margrit Hollborn, Peter Wiedemann, Andreas Bringmann
Purpose: Systemic hypertension is a risk factor of neovascular age-related macular degeneration; consumption of dietary salt resulting in extracellular hyperosmolarity is a main cause of hypertension. Extracellular hyperosmolarity was shown to induce expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), in RPE cells. The aim of the present study was to determine whether the hyperosmotic expression of growth factor genes in RPE cells is mediated by activator protein-1 (AP-1), and whether c-Fos and c-Jun genes are regulated by extracellular osmolarity...
2018: Molecular Vision
Eva B Nygaard, Cathrine Ørskov, Thomas Almdal, Henrik Vestergaard, Birgitte Andersen
Fibroblast growth factor 21 (FGF21) is a metabolic regulator of energy and lipid metabolism. FGF21 is highly expressed in liver while FGF21 receptors (beta-klotho (KLB) and FGFR1c) are highly expressed in white adipose tissues (WATs). Plasma FGF21 has been shown to be increased after 7–10 days of fasting but oppositely plasma FGF21 is also increased in obesity. The aim of this study was to measure the effect of 60 h of fasting on plasma FGF21 levels in obese and lean subjects and to determine the gene expression of KLB and FGFR1c in the subcutaneous WAT before, during and after 60 h of fasting...
October 1, 2018: Journal of Endocrinology
Kirollos S Hanna
Urothelial Carcinoma (UC) is the second most common malignancy of the genitourinary system and is the sixth most common cancer in the USA. Over a decade prior to 2016, the standard of care for early disease consisted of transuretheral resection of the bladder tumor with or without intravesicular chemotherapy or immunotherapy. Systemic chemotherapies such as gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, cisplatin were reserved for recurrent, muscle-invasive, advanced or metastatic disease...
October 10, 2018: Journal of Oncology Pharmacy Practice
Tim H Holmström, Anu-Maarit Moilanen, Tarja Ikonen, Mari L Björkman, Tero Linnanen, Gerd Wohlfahrt, Stefan Karlsson, Riikka Oksala, Timo Korjamo, Susanta Samajdar, Srinivasan Rajagopalan, Shekar Chelur, Kishore Narayan, Raghuveer K Ramachandra, Jiju Mani, Rashmi Nair, Nagaraj Gowda, Thomas Anthony, Samiulla Dhodheri, Subhendu Mukherjee, Ravi K Ujjinamatada, Nanduri Srinivas, Murali Ramachandra, Pekka J Kallio
Alterations in the gene encoding for the fibroblast growth factor receptor (FGFR) and upregulation of the vascular endothelial growth factor receptor (VEGFR) are found often in cancer, which correlate with disease progression and unfavorable survival. Additionally, FGFR and VEGFR signaling synergistically promote tumor angiogenesis, and activation of FGFR signaling has been described as functional compensatory angiogenic signal following development of resistance to VEGFR inhibition. Several selective small-molecule FGFR kinase inhibitors are currently in clinical development...
October 9, 2018: Molecular Cancer Therapeutics
Zhongji Han, Zhousheng Xiao, Kamyar Kalantar-Zadeh, Hamid Moradi, Tariq Shafi, Sushrut S Waikar, L Darryl Quarles, Zhi Yu, Adrienne Tin, Josef Coresh, Csaba P Kovesdy
End stage renal disease (ESRD) is characterized by complex metabolic abnormalities, yet the clinical relevance of specific biomarkers remains unclear. The development of multiplex diagnostic platforms is creating opportunities to develop novel diagnostic and therapeutic approaches. SOMAscan is an innovative multiplex proteomic platform which can measure >1300 proteins. In the present study, we performed SOMAscan analysis of plasma samples and validated the measurements by comparison with selected biomarkers...
October 8, 2018: Diagnostics
Terry L Ng, Hui Yu, Derek E Smith, Theresa A Boyle, Emily R York, Scott Leedy, Dexiang Gao, Dara L Aisner, Adrie Van Bokhoven, Lynn E Heasley, Fred R Hirsch, D Ross Camidge
INTRODUCTION: Preclinically, high epidermal growth factor receptor 1 (FGFR1) messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell lung cancer and small-cell lung cancer cell lines. KRAS mutations did not preclude sensitivity. PATIENTS AND METHODS: Metastatic EGFR- and ALK-negative lung cancers were screened for FGFR1-MRNA by in-situ hybridization (ISH) and FGFR1-AMP by silver in-situ hybridization (SISH)...
September 7, 2018: Clinical Lung Cancer
Jinfang Bao, Yingfeng Shi, Min Tao, Na Liu, Shougang Zhuang, Weijie Yuan
Autophagy has been identified as a cellular process of bulk degradation of cytoplasmic components and its persistent activation is critically involved in the renal damage induced by ureteral obstruction. However, the role and underlying mechanisms of autophagy in hyperuricemic nephropathy (HN) remains unknown. In this study, we observed that inhibition of autophagy by 3-methyladenine (3-MA) abolished uric acid-induced differentiation of renal fibroblasts to myofibroblasts and activation of transforming growth factor-β1 (TGF-β1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways in cultured renal interstitial fibroblasts...
October 7, 2018: Clinical Science (1979-)
Michael J Boyer, Satoru Eguchi
Hypertension is a significant risk factor for the development of cardiovascular ailments, including ischemic heart disease and diastolic dysfunction. In a recent issue of Clinical Science , Li et al. [ Clin. Sci. (2018) 132 , 1855-1874] report that β-2 microglobulin (β2M) is a novel secreted soluble factor released by cardiac myocytes during pressure overload that promotes profibrotic gene expression in cardiac fibroblasts both in vitro and in vivo Their study further identifies elevated β2M levels as a possible biomarker for hypertensive patients with cardiac complications...
October 15, 2018: Clinical Science (1979-)
Margherita Leonardi, Eluisa Perna, Serena Tronnolone, David Colecchia, Mario Chiariello
Macroautophagy/autophagy is one of the major responses to stress in eukaryotic cells and is implicated in several pathological conditions such as infections, neurodegenerative diseases and cancer. Interestingly, cancer cells take full advantage of autophagy both to support tumor growth in adverse microenvironments and to oppose damages induced by anti-neoplastic therapies. Importantly, different human oncogenes are able to modulate this survival mechanism to support the transformation process, ultimately leading to 'autophagy addiction'...
October 5, 2018: Autophagy
Kei Otsuka, Asuka Takehara, Natsuko Chiba, Yasuhisa Matsui
Primordial germ cells (PGCs) are precursors of eggs and sperm. Although PGCs are unipotent cells in vivo, they are reprogrammed into pluripotent stem cells (PSCs), also known as embryonic germ cells (EGCs), in the presence of leukemia inhibitory factor and basic fibroblast growth factor (bFGF) in vitro. However, the molecular mechanisms responsible for their reprogramming are not fully understood. Here we show identification of transcription factors that mediate PGC reprogramming. We selected genes encoding transcription factors or epigenetic regulatory factors whose expression was significantly different between PGCs and PSCs with in silico analysis and RT-qPCR...
2018: PloS One
Wei Na, Jia-Qiang Yu, Zi-Chun Xu, Xin-Yang Zhang, Li-Li Yang, Zhi-Ping Cao, Hui Li, Hui Zhang
Selection for rapid growth in chickens has always been accompanied by increased fat deposition and excessive fat deposition, especially abdominal fat, cannot only decrease feed efficiency but also cause many diseases. Finding the candidate genes associated with abdominal fat deposition is essential for breeding. To identify these candidate genes, we applied linkage disequilibrium and selection signature analysis using chicken 60 k single nucleotide polymorphism (SNP) chips in two broiler lines divergently selected for abdominal fat content for 11 generations...
October 4, 2018: Poultry Science
Kelsey E Murphy, Killian Llewellyn, Samuel Wakser, Josef Pontasch, Natasha Samanich, Matthew Flemer, Kenneth Hensley, Dong-Shik Kim, Joshua J Park
Oxidative stress triggers and exacerbates neurodegeneration in Alzheimer's disease (AD). Various antioxidants reduce oxidative stress, but these agents have little efficacy due to poor blood-brain barrier (BBB) permeability. Additionally, single-modal antioxidants are easily overwhelmed by global oxidative stress. Activating nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its downstream antioxidant system are considered very effective for reducing global oxidative stress. Thus far, only a few BBB-permeable agents activate the Nrf2-dependent antioxidant system...
October 3, 2018: Journal of Biological Chemistry
Lifan Zhu, Zhen Weng, Pengcheng Shen, Jianxin Zhou, Jincai Zeng, Fengbiao Weng, Xiaojian Zhang, Huilin Yang
The present study aimed to investigate the role of S100B in the inflammation process during osteoarthritis (OA). OA cartilage samples were collected for S100B expression analysis. S100B expression levels were significantly increased in patients with OA compared with the Controls (1.28±0.66 vs. 0.42±0.31; P=0.01) and were determined to be correlated with TNF‑α (r=0.42; P=0.04) and IL‑1β (r=0.73; P=0.001) expression levels. Orthopedic casting tape was used to immobilize the right knee at 180˚ extension of adult female New Zealand white rabbits for 4 weeks to establish an OA model...
October 1, 2018: Molecular Medicine Reports
Min Wang, Christian Wiraja, Meiling Wee, David Yeo, Lianzhe Hu, Chenjie Xu
Identification of abnormal scars at their early stage has attracted increasing attentions as the scars can only be assessed qualitatively and subjectively upon maturity, when no invasive procedure is involved. This report introduces a fluorescent probe that targets a potential abnormal scar biomarker (connective tissue growth factor (CTGF) mRNA) in skin fibroblasts. This probe is constructed of hairpin-structured probes (HPs) targeting CTGF mRNA and the nano-graphene oxide (nano-GO) base. The HPs are non-covalently absorbed on the surface of nano-GO, which pre-quenches the fluorescence of HPs...
December 14, 2018: Analytica Chimica Acta
Felix Harpain, Mohamed A Ahmed, Xenia Hudec, Gerald Timelthaler, Gerd Jomrich, Leonhard Müllauer, Edgar Selzer, Wolfgang Dörr, Michael Bergmann, Klaus Holzmann, Bettina Grasl-Kraupp, Michael Grusch, Walter Berger, Brigitte Marian, Gerd R Silberhumer
PURPOSE: Therapy response to neoadjuvant radiochemotherapy (nRCT) of locally advanced rectal cancer varies widely so that markers predicting response are urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling is involved in pro-survival signaling and thereby may result in radiation resistance. METHODS: In a cohort of 43 rectal cancer patients, who received nRCT, we analyzed protein levels of FGF 8 and its downstream target Survivin by immunohistochemistry to assess their impact on nRCT response...
October 1, 2018: Journal of Cancer Research and Clinical Oncology
Stefanie Worsch, Mathias Heikenwalder, Hans Hauner, Bernhard L Bader
Background: We previously reported on the anti-obesogenic and anti-inflammatory effects associated with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in our diet-induced obesity (DIO) mouse model. Two isocaloric high-fat diets (HFDs; 48 kJ% fat), HFD (HF) and n-3 LCPUFA-enriched HFD (HF/n-3), and a control diet (C; 13 kJ% fat) were used. The underlying mechanisms however have largely remained unclear. Here, we assessed whether the reduced fat mass reflected n-3 LCPUFA-induced expression changes in lipid metabolism of the intestine, liver, and interscapular brown adipose tissue (iBAT), as well as increased iBAT thermogenic capacity...
2018: Nutrition & Metabolism
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
BACKGROUND: Genetic alterations occurring in lung cancer are the basis for defining molecular subtypes and essential for targeted therapies. Exhaled breath condensate (EBC) is a form of non-invasive sample that, amongst components, contains DNA from pulmonary tissue. Next-generation sequencing (NGS) was herein used to analyze mutations in EBC from patients with lung cancer. MATERIALS AND METHODS: EBC was collected from 26 patients with cancer and 20 healthy controls...
October 2018: Anticancer Research
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