Read by QxMD icon Read


Yang Liu, Xia Peng, Xiaocong Guan, Dong Lu, Yong Xi, Shiyu Jin, Hui Chen, Limin Zeng, Jing Ai, Meiyu Geng, Youhong Hu
FGF receptors (FGFRs) are tyrosine kinases that are overexpressed in diverse tumors by genetic alterations such as gene amplifications, somatic mutations and translocations. Owing to this characteristic, FGFRs are attractive targets for cancer treatment. It has been demonstrated that most multi-targeted, ATP competitive tyrosine kinase inhibitors are active against FGFRs as well as other kinases. The design of new and more selective inhibitors of FGFRs, which might be reduced off-target and side effects, is a difficult yet significant challenge...
October 4, 2016: European Journal of Medicinal Chemistry
Giustina Ferone, Ji-Ying Song, Kate D Sutherland, Rajith Bhaskaran, Kim Monkhorst, Jan-Paul Lambooij, Natalie Proost, Gaetano Gargiulo, Anton Berns
Lung squamous cell carcinoma (LSCC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Therefore, preclinical models mimicking its salient features are urgently needed. Here we describe mouse models bearing various combinations of genetic lesions predominantly found in human LSCC. We show that SOX2 but not FGFR1 overexpression in tracheobronchial basal cells combined with Cdkn2ab and Pten loss results in LSCC closely resembling the human counterpart. Interestingly, Sox2;Pten;Cdkn2ab mice develop LSCC with a more peripheral location when Club or Alveolar type 2 (AT2) cells are targeted...
October 10, 2016: Cancer Cell
Yongkun Sun, Wei Niu, Feng Du, Chunxia Du, Shuting Li, Jinwan Wang, Li Li, Fengqing Wang, Yu Hao, Chuan Li, Yihebali Chi
BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. METHODS: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1)...
October 4, 2016: Journal of Hematology & Oncology
M Phan, F Conte, K D Khandelwal, C W Ockeloen, T Bartzela, T Kleefstra, H van Bokhoven, M Rubini, H Zhou, C E L Carels
Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts, to gain insight into the molecular mechanisms underlying their dual involvement in the development of teeth and facial primordia...
December 2016: Human Genetics
G Avallone, V Pellegrino, P Roccabianca, E Lepri, L Crippa, G Beha, L De Tolla, G Sarli
The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP...
October 3, 2016: Veterinary Pathology
Min Ye, Weiqin Lu, Xiaojie Wang, Cong Wang, James L Abbruzzese, Guang Liang, Xiaokun Li, Yongde Luo
The anti-obese and anti-diabetic FGF21 regulates lipid metabolism and energy homeostasis by targeting the betaKlotho-FGFR1 binary complex in adipose tissue adipocytes. Since lipid droplet is the organelle responsible for storing lipid energy in adipocytes, it is the plausible target of FGF21 action. However, the impact of the FGF21-betaKlotho-FGFR1 signaling pathway on the functions of the lipid droplet is not clearly understood. Using our mouse models of adipocyte-specific FGFR1 ablation and hepatic overexpression of FGF21 with diet-induced obesity established previously, we analyzed the alterations of the pathways involved in energy and substrate metabolism that is attributable to the dynamic functions of the lipid droplet...
October 3, 2016: Endocrinology
Tale Barøy, Chandra S R Chilamakuri, Susanne Lorenz, Jinchang Sun, Øyvind S Bruland, Ola Myklebost, Leonardo A Meza-Zepeda
Osteosarcoma (OS) is the most common primary malignant tumor of bone, showing complex chromosomal rearrangements but with few known consistent changes. Deeper biological understanding is crucial to find new therapies to improve patient survival. We have sequenced the whole exome of two primary tumors (before and after chemotherapy), one metastatic tumor and a matched normal sample from two OS patients, to identify mutations involved in cancer biology. The metastatic samples were also RNA sequenced. By RNA sequencing we identified dysregulated expression levels of drug resistance- and apoptosis-related genes...
2016: PloS One
Akira Ohishi, Gen Nishimura, Fumiko Kato, Hiroyuki Ono, Kaori Maruwaka, Mako Ago, Hiroshi Suzumura, Etsuko Hirose, Yuki Uchida, Maki Fukami, Tsutomu Ogata
Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed FGFR1-3 genes in four patients with Crouzon syndrome (CS), four patients with Pfeiffer syndrome type 2 (PS-2), one patient with Jackson-Weiss syndrome (JWS), and two patients (sisters) with Muenke syndrome (MS). FGFR2 and FGFR3 mutations were identified in 10 of the 11 patients. Notably, we found a novel FGFR2 p.Asn549Thr mutation in a patient with CS, and a novel FGFR2 p.Ser347Cys mutation in a patient with JWS (thus, this patient was turned out to have an FGFR2-related PS-variant)...
September 28, 2016: American Journal of Medical Genetics. Part A
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
Fibroblast growth factor 21 (FGF21) has a significant role in the regulation of energy metabolism, e.g., in the control of systemic glucose and lipid metabolism. For instance, FGF21 enhances insulin sensitivity, increases glucose uptake, and thus can decrease serum hyperglycemia, while it also increases lipid oxidation and inhibits lipogenesis. AMP-activated protein kinase (AMPK) is a tissue energy sensor involved in maintaining the energy balance and tissue integrity. It is known that AMPK signaling generates an energy metabolic profile which displays a remarkable overlap with that of FGF21...
September 27, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
D Fumagalli, T R Wilson, R Salgado, X Lu, J Yu, C O'Brien, K Walter, L Y Huw, C Criscitiello, I Laios, V Jose, D N Brown, F Rothé, M Maetens, D Zardavas, P Savas, D Larsimont, M J Piccart-Gebhart, S Michiels, M R Lackner, C Sotiriou, S Loi
BACKGROUND: Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy. MATERIALS AND METHODS: A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Elie Traer, Jacqueline Martinez, Nathalie Javidi-Sharifi, Anupriya Agarwal, Jennifer Dunlap, Isabel English, Tibor Kovacsovics, Jeffrey W Tyner, Melissa Wong, Brian J Druker
Potent FLT3 inhibitors such as quizartinib (AC220) have shown promise in treating acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of resistance whereby extrinsic microenvironmental proteins FLT3 ligand (FL) and fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation of ligand-independent resistance mechanisms...
September 26, 2016: Cancer Research
Philipp H Baldia, Angela Maurer, Timon Heide, Michael Rose, Robert Stoehr, Arndt Hartmann, Sarah V Williams, Margaret A Knowles, Ruth Knuechel, Nadine T Gaisa
Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis)...
September 22, 2016: Oncotarget
S R Mishra, N Thakur, A Somal, M S Parmar, R Reshma, G Rajesh, V P Yadav, M K Bharti, Jaya Bharati, A Paul, V S Chouhan, G T Sharma, G Singh, M Sarkar
The present study investigated the expression and localization of FGF and its functional receptors in the follicle of buffalo and the treatment of FGF2 on mRNA expression of CYP19A1 (aromatase), PCNA, and BAX (BCL-2 associated X protein) in cultured buffalo granulosa cells (GCs). Follicles were classified into four groups based on size and E2 level in follicular fluid (FF): F1, 4-6mm diameter, E2<0.5ng/ml of FF; F2, 7-9mm, E2=0.5-5ng/ml; F3, 10-13mm, E2=5-40ng/ml; F4, >14mm, E2>180ng/ml. The qPCR studies revealed that the mRNA expression of FGF1, FGF2 and FGF7 were maximum (P<0...
October 2016: Research in Veterinary Science
Shada J Alabed, Mohammad Khanfar, Mutasem O Taha
AIM: FGFR-1 is an oncogenic kinase involved in several cancers. FGFR1-specific inhibitors have shown promising results against several human cancers prompting us to model this interesting target. Toward the end, we implemented elaborate ligand-based and structure-based computational workflows to explore the pharmacophoric requirements for potent FGFR-1 inhibitors. Results & methodology: Structure-based and ligand-based modeling applied on 59 diverse FGFR-1 inhibitors yielded novel pharmacophore and quantitative structure-activity relationship models that were used to scan the National Cancer Institute's structural database for novel leads...
September 19, 2016: Future Medicinal Chemistry
Jin Nishino, Miwa Yamazaki, Masanobu Kawai, Kanako Tachikawa, Keiko Yamamoto, Kazuaki Miyagawa, Mikihiko Kogo, Keiichi Ozono, Toshimi Michigami
Dentin matrix protein 1 (DMP1) is an extracellular matrix protein involved in phosphate metabolism and biomineralization, and its expression markedly increases during the maturation of osteoblasts into osteocytes. We previously reported that an increased level of inorganic phosphate (Pi) in media up-regulated the expression of Dmp1 in primary osteocytes isolated from mouse bones. In the present study, we found that elevated extracellular Pi strongly induced the expression of Dmp1 in osteoblasts and explored its underlying mechanism of action...
September 17, 2016: Journal of Cellular Biochemistry
Terence G Hall, Yi Yu, Sudharshan Eathiraj, Yunxia Wang, Ronald E Savage, Jean-Marc Lapierre, Brian Schwartz, Giovanni Abbadessa
Dysregulation of Fibroblast Growth Factor Receptor (FGFR) signaling through amplifications, mutations, and gene fusions has been implicated in a broad array of cancers (e.g. liver, gastric, ovarian, endometrial, and bladder). ARQ 087 is a novel, ATP competitive, small molecule, multi-kinase inhibitor with potent in vitro and in vivo activity against FGFR addicted cell lines and tumors. Biochemically, ARQ 087 exhibited IC50 values of 1.8 nM for FGFR2, and 4.5 nM for FGFR1 and 3. In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2α, AKT, ERK) was evident by the response to ARQ 087 treatment...
2016: PloS One
Weili Miao, Yongsheng Xiao, Lei Guo, Xiaogang Jiang, Ming Huang, Yinsheng Wang
Kinases are one of the most important families of enzymes that are involved in numerous cell signaling processes. Existing methods for studying kinase expression and activation have limited kinome coverage. Herein we established a multiple-reaction monitoring (MRM)-based targeted proteomic method that provided an unprecedented coverage (∼80%) of the human kinome. We employed this method for profiling comprehensively the alterations of the global kinome of HEK293T human embryonic kidney cells upon treatment with methylglyoxal, a glycolysis byproduct that is present at elevated levels in blood and tissues of diabetic patients and is thought to contribute to diabetic complications...
October 4, 2016: Analytical Chemistry
Frank Y Lin, Katie Bergstrom, Richard Person, Abhishek Bavle, Leomar Y Ballester, Sarah Scollon, Robin Raesz-Martinez, Andrew Jea, Sherri Birchansky, David A Wheeler, Stacey L Berg, Murali M Chintagumpala, Adekunle M Adesina, Christine Eng, Angshumoy Roy, Sharon E Plon, D Williams Parsons
The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p...
September 2016: Cold Spring Harbor Molecular Case Studies
Daichao Wu, Ming Guo, Michael A Philips, Lingzhi Qu, Longying Jiang, Jun Li, Xiaojuan Chen, Zhuchu Chen, Lin Chen, Yongheng Chen
Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2...
2016: PloS One
Bei Xu, Quansheng Jin, Jun Zeng, Ting Yu, Yan Chen, Shuangzhi Li, Daoqiong Gong, Lili He, Xiaoyue Tan, Li Yang, Gu He, Jinhui Wu, Xiangrong Song
A rational combination is critical to achieve efficiently synergistic therapeutic efficacy for tumor treatment. Hence, we designed novel antitumor combinations (T-NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with antiangiogenesis/antitumor agents. The truncated bFGF peptide (tbFGF), which could effectively bind to FGFR1 overexpressed on tumor neovasculature endothelial cells and tumor cells, was selected to modify PLGA nanoparticles (D/P-NPs) simultaneously loaded with PEDF gene and paclitaxel in this study...
October 5, 2016: ACS Applied Materials & Interfaces
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"