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Sameer Agnihotri, Shahrzad Jalali, Mark R Wilson, Arnavaz Danesh, Mira Li, George Klironomos, Jonathan R Krieger, Alireza Mansouri, Osaama Khan, Yasin Mamatjan, Natalie Landon-Brace, Takyee Tung, Mark Dowar, Tiantian Li, Jeffrey P Bruce, Kelly E Burrell, Peter D Tonge, Amir Alamsahebpour, Boris Krischek, Pankaj Kumar Agarwalla, Wenya Linda Bi, Ian F Dunn, Rameen Beroukhim, Michael G Fehlings, Vera Bril, Stefano M Pagnotta, Antonio Iavarone, Trevor J Pugh, Kenneth D Aldape, Gelareh Zadeh
Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19-Mb chromosomal inversion on chromosome 10q...
October 10, 2016: Nature Genetics
Zakaria Ezzoukhry, Elodie Henriet, Léo Piquet, Kevin Boyé, Paulette Bioulac-Sage, Charles Balabaud, Gabrielle Couchy, Jessica Zucman-Rossi, Violaine Moreau, Frédéric Saltel
Transforming growth factor-β1 (TGF-β1) is an important player in chronic liver diseases inducing fibrogenesis and hepatocellular carcinoma (HCC) development. TGF-β1 promotes pleiotropic modifications at the cellular and matrix microenvironment levels. TGF-β1 was described to enhance production of type I collagen and its associated cross-linking enzyme, the lysyl oxidase-like2 (LOXL2). In addition, TGF-β1 and type I collagen are potent inducers of invadosomes. Indeed, type I collagen fibers induce the formation of active linear invadosomes through the discoidin domain receptor 1 (DDR1)...
October 4, 2016: European Journal of Cell Biology
Angelica Macauda, Diego Calvetti, Giuseppe Maccari, Kari Hemminki, Asta Försti, Hartmut Goldschmidt, Niels Weinhold, Richard Houlston, Vibeke Andersen, Ulla Vogel, Gabriele Buda, Judit Varkonyi, Anna Sureda, Joaquin Martinez Lopez, Marzena Watek, Aleksandra Butrym, Maria Eugenia Sarasquete, Marek Dudziński, Artur Jurczyszyn, Agnieszka Druzd-Sitek, Marcin Kruszewski, Edyta Subocz, Mario Petrini, Elzbieta Iskierka-Jażdżewska, Malgorzata Raźny, Gergely Szombath, Herlander Marques, Daria Zawirska, Dominik Chraniuk, Janusz Halka, Svend Erik Hove Jacobsen, Grzegorz Mazur, Ramón García Sanz, Charles Dumontet, Victor Moreno, Anna Stępień, Katia Beider, Matteo Pelosini, Rui Manuel Reis, Malgorzata Krawczyk-Kulis, Marcin Rymko, Hervé Avet-Loiseau, Fabienne Lesueur, Norbert Grząśko, Olga Ostrovsky, Krzysztof Jamroziak, Annette J Vangsted, Andrés Jerez, Waldemar Tomczak, Jan Maciej Zaucha, Katalin Kadar, Juan Sainz Pérez, Arnon Nagler, Stefano Landi, Federica Gemignani, Federico Canzian
Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression...
October 8, 2016: International Journal of Cancer. Journal International du Cancer
Hong-Jie Zhu, Yong-Ming Yan, Zheng-Chao Tu, Jin-Feng Luo, Rui Liang, Tong-Hua Yang, Yong-Xian Cheng, Shu-Mei Wang
Plancyamides A (1) and B (3), plancypyrazine A (2), and plancyols A (4) and B (5), five new compounds (1-5), and three known ones (6-8), were isolated from the whole bodies of Polyphaga plancyi Bolivar. Their structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Among them, compound 3 is racemic, chiral HPLC separation afforded its respective enantiomers. The absolute configuration of 1 was assigned by computational methods. Biological evaluation of all the compounds with exception of 7 and 8 discloses that compounds 2 and 4 could inhibit JAK3 kinase with IC50 values of 12...
October 2016: Fitoterapia
Zhi-Ming Wang, Hui-Yuan Wen, Dong-Sheng Yang, Ming Ye, Ying Ma, Li-Ping Zhang
PURPOSE: To investigate the expression and significance of discoidin domain receptor 1 (DDR1) in salivary gland mucoepidermoid carcinoma (MEC). METHODS: Immunohistochemical and Western blot method were used to detect the expression of DDR1 in MEC M3SP2 and MC3 cell lines. Immunohistochemical method was used to detect the expression of DDR1 in 58 MEC and 20 normal salivary gland tissues. SPSS 13.0 software package was used for statistical analysis. RESULTS: The positive expression rate of DDR1 in salivary gland MEC tissues was 79...
June 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
Huocong Huang, Robert A Svoboda, Audrey J Lazenby, Jintana Saowapa, Nina Chaika, Ke Ding, Margaret J Wheelock, Keith R Johnson
Pancreatic ductal adenocarcinomas (PDAC) are highly malignant cancers characterized by extensive invasion into surrounding tissues, metastasis to distant organs, and a limited response to therapy. A main feature of PDAC is desmoplasia, which leads to extensive deposition of collagen I. We have demonstrated that collagen I can induce epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. A hallmark of EMT is an increase in the expression of the mesenchymal cadherin N-cadherin. Previously we showed up-regulation of N-cadherin promotes tumor cell invasion and collagen I-induced EMT is mediated by two collagen receptors, alpha2beta1-integrin and discoidin domain receptor 1 (DDR1)...
September 7, 2016: Journal of Biological Chemistry
Lu Liu, Muzammal Hussain, Jinfeng Luo, Anna Duan, Chaonan Chen, Zhengchao Tu, Jiancun Zhang
Novel dasatinib analogues as DDR1 and DDR2 inhibitors were designed and synthesized. The synthesized compounds were screened for DDR1 and DDR2 kinase inhibitory and cancer cell proliferation inhibitory activities. Some of the compounds showed the potent inhibitory activities against both DDR1 and DDR2, as well as anticancer activity in low nanomolar range against K562 cell line; especially, compound 3j demonstrated significantly better inhibitory potency than the parental dasatinib against both DDRs and also demonstrated the potent inhibitory activity against K562 cell lines (IC50 values of 2...
September 2, 2016: Chemical Biology & Drug Design
(no author information available yet)
TM4SF1 induces noncanonical DDR1 signaling to reactivate disseminated breast cancer cells.
September 2016: Cancer Discovery
Mohammed-Amine El Azreq, Maleck Kadiri, Marc Boisvert, Nathalie Pagé, Philippe A Tessier, Fawzi Aoudjit
Effector T cell migration through the tissue extracellular matrix (ECM) is an important step of the adaptive immune response and in the development of inflammatory diseases. However, the mechanisms involved in this process are still poorly understood. In this study, we addressed the role of a collagen receptor, the discoidin domain receptor 1 (DDR1), in the migration of Th17 cells. We showed that the vast majority of human Th17 cells express DDR1 and that silencing DDR1 or using the blocking recombinant receptor DDR1:Fc significantly reduced their motility and invasion in three-dimensional (3D) collagen...
July 6, 2016: Oncotarget
Silvia Avino, Paola De Marco, Francesca Cirillo, Maria Francesca Santolla, Ernestina Marianna De Francesco, Maria Grazia Perri, Damiano Rigiracciolo, Vincenza Dolce, Antonino Belfiore, Marcello Maggiolini, Rosamaria Lappano, Adele Vivacqua
Insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) system has been largely involved in the pathogenesis and development of various tumors. We have previously demonstrated that IGF-IR cooperates with the G-protein estrogen receptor (GPER) and the collagen receptor discoidin domain 1 (DDR1) that are implicated in cancer progression. Here, we provide novel evidence regarding the molecular mechanisms through which IGF-I/IGF-IR signaling triggers a functional cross-talk with GPER and DDR1 in both mesothelioma and lung cancer cells...
June 30, 2016: Oncotarget
Hua Gao, Goutam Chakraborty, Zhanguo Zhang, Intissar Akalay, Mayur Gadiya, Yaquan Gao, Surajit Sinha, Jian Hu, Cizhong Jiang, Muzaffar Akram, Edi Brogi, Birgit Leitinger, Filippo G Giancotti
Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKCα. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives metastatic reactivation in the lung, bone, and brain...
June 30, 2016: Cell
Jeffrey R Tonniges, Benjamin Albert, Edward P Calomeni, Shuvro Roy, Joan Lee, Xiaokui Mo, Susan E Cole, Gunjan Agarwal
The quantity and quality of collagen fibrils in the extracellular matrix (ECM) have a pivotal role in dictating biological processes. Several collagen-binding proteins (CBPs) are known to modulate collagen deposition and fibril diameter. However, limited studies exist on alterations in the fibril ultrastructure by CBPs. In this study, we elucidate how the collagen receptor, discoidin domain receptor 1 (DDR1) regulates the collagen content and ultrastructure in the adventitia of DDR1 knock-out (KO) mice. DDR1 KO mice exhibit increased collagen deposition as observed using Masson's trichrome...
June 2016: Microscopy and Microanalysis
Violaine Moreau, Frédéric Saltel
Accumulation of type I collagen fibrils in tumors is associated with an increased risk of metastasis. We recently demonstrated that the collagen sensor discoidin domain receptor 1 (DDR1) interacts with type I collagen fibrils to allow proteolysis-based cancer cell invasion through the formation of a new class of invadosomes, termed linear invadosomes.
October 2015: Molecular & Cellular Oncology
Antonina Frolov, Ian M Evans, Ningning Li, Kastytis Sidlauskas, Ketevan Paliashvili, Nicola Lockwood, Angela Barrett, Sebastian Brandner, Ian C Zachary, Paul Frankel
Imatinib was the first targeted tyrosine kinase inhibitor to be approved for clinical use, and remains first-line therapy for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. We show that treatment of human glioblastoma multiforme (GBM) tumour cells with imatinib and the closely-related drug, nilotinib, strikingly increases tyrosine phosphorylation of p130Cas, focal adhesion kinase (FAK) and the downstream adaptor protein paxillin (PXN), resulting in enhanced cell migration and invasion...
2016: Scientific Reports
Scott M Haake, Jiannong Li, Yun Bai, Fumi Kinose, Bin Fang, Eric A Welsh, Roy Zent, Jasreman Dhillon, Julio M Pow-Sang, Y Ann Chen, John M Koomen, W Kimryn Rathmell, Mayer Fishman, Eric B Haura
PURPOSE: Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes. EXPERIMENTAL DESIGN: Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. In order to describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry-based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors...
May 24, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zhen Wang, Huan Bian, Sergio G Bartual, Wenting Du, Jinfeng Luo, Hu Zhao, Shasha Zhang, Cheng Mo, Yang Zhou, Yong Xu, Zhengchao Tu, Xiaomei Ren, Xiaoyun Lu, Rolf A Brekken, Libo Yao, Alex N Bullock, Jin Su, Ke Ding
The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.
June 23, 2016: Journal of Medicinal Chemistry
Ruixia Xie, Xiaoying Wang, Guoqing Qi, Zhiping Wu, Rong Wei, Peirong Li, Dekui Zhang
In this study, we investigated the effects of DDR1 on the invasion and metastasis in gastric cancer (GC) via epithelial-mesenchymal transition (EMT). Immunohistochemistry analysis was used to detect DDR1, E-cadherin, and Vimentin expression in GC tissues as well as DDR1 expression in GC cell lines and normal gastric epithelial cells. The relationship between DDR1 expression and EMT in GC cell lines was explored by down and upregulating DDR1 and examining corresponding changes in the expression of EMT-related proteins and in biological characteristics...
May 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jingyuan Song, Xiao Chen, Jin Bai, Qinghua Liu, Hui Li, Jianwan Xie, Hui Jing, Junnian Zheng
Discoidin domain receptor I (DDR1) is confirmed as a receptor tyrosine kinase (RTK), which plays a consequential role in a variety of cancers. Nevertheless, the influence of DDR1 expression and development in renal clear cell carcinoma (RCCC) are still not well corroborated. In our research, we firstly discovered that the expression level of DDR1 was remarkable related to TNM stage (p = 0.032), depth of tumor invasion (p = 0.047), and lymph node metastasis (p = 0.034) in 119 RCCC tissue samples using tissue microarray...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hassan Rammal, Charles Saby, Kevin Magnien, Laurence Van-Gulick, Roselyne Garnotel, Emilie Buache, Hassan El Btaouri, Pierre Jeannesson, Hamid Morjani
The extracellular matrix critically controls cancer cell behavior by inducing several signaling pathways through cell membrane receptors. Besides conferring structural properties to tissues around the tumor, the extracellular matrix is able to regulate cell proliferation, survival, migration, and invasion. Among these receptors, the integrins family constitutes a major class of receptors that mediate cell interactions with extracellular matrix components. Twenty years ago, a new class of extracellular matrix receptors has been discovered...
2016: Frontiers in Pharmacology
Can Chen, Jingjing Deng, Xiaoping Yu, Fengbo Wu, Ke Men, Qian Yang, Yanfeng Zhu, Xiaogang Liu, Qinglin Jiang
Idiopathic pulmonary fibrosis (IPF) is a kind of a chronic and fatal lung disease leading to progressive lung function decline. Although several RNA microarray studies on IPF patients have been reported, their results were merely specific to each study with distinct platforms or sample types. In the current study, an integrative transcriptome meta-analysis of IPF was performed to explore regulated pathways, based on four independent expression profiling microarrays of IPF datasets, including 73 samples from IPF tissues or lung fibroblast cells...
April 26, 2016: Molecular BioSystems
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