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Aude Dorison, Christos Chantziantoniou
Discoidin Domain Receptor 1 (DDR1) belongs to a family of two non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. DDR1 has been widely studied in different kind of pathologies including chronic kidney diseases (CKD). The aims of this commentary are 1. to review the existing information about DDR1 expression in healthy and diseased kidney, 2. to comment the data highlighting DDR1 as a major actor in CKD, 3. to suggest areas of research which require further investigation to better characterize the signaling pathways regulating DDR1 role in CKD...
February 19, 2018: Cell Adhesion & Migration
Laura Lacerda Coelho, Isabela Resende Pereira, Mirian Claudia de Souza Pereira, Liliane Mesquita, Joseli Lannes-Vieira, Daniel Adesse, Luciana Ribeiro Garzoni
BACKGROUND: Cardiac fibrosis is a consequence of chronic chagasic cardiomyopathy (CCC). In other cardiovascular diseases, the protagonist role of fibroblasts in cardiac fibrosis is well established. However, the role of cardiac fibroblasts (CFs) in fibrosis during the CCC is not clear. Here, our aim was to investigate the effect of Trypanosoma cruzi, the etiological agent of Chagas disease on CFs activation. METHODS: Cardiac fibroblasts were purified from primary cultures of mouse embryo cardiac cells...
January 30, 2018: Parasites & Vectors
Eleonora Bonaparte, Chiara Pesenti, Laura Fontana, Rossella Falcone, Leda Paganini, Anna Marzorati, Stefano Ferrero, Mario Nosotti, Paolo Mendogni, Claudia Bareggi, Silvia Maria Sirchia, Silvia Tabano, Silvano Bosari, Monica Miozzo
BACKGROUND: Identification of predictive molecular alterations in lung adenocarcinoma is essential for accurate therapeutic decisions. Although several molecular approaches are available, a number of issues, including tumor heterogeneity, frequent material scarcity, and the large number of loci to be investigated, must be taken into account in selecting the most appropriate technique. MALDI-TOF mass spectrometry (MS), which allows multiplexed genotyping, has been adopted in routine diagnostics as a sensitive, reliable, fast, and cost-effective method...
January 12, 2018: Diagnostic Pathology
Huan Bian, Xiaowei Nie, Xin Bu, Feng Tian, Libo Yao, Jingyu Chen, Jin Su
The most typical structural feature of human interstitial lung diseases (ILDs) is the accumulation of vast amounts of collagens within the lung interstitium. The membrane receptors that are responsible for recognising collagens and then transducing signals into the cells include four members of the integrin family (α1β1, α2β1, α10β1 and α11β1) and two members of the discoidin domain receptor family (DDR1 and DDR2). However, it remains unknown whether these six collagen receptors similarly contribute to the pathogenesis of fibrotic lung diseases...
January 2018: ERJ Open Research
Whitney R Grither, Laura M Divine, Eric H Meller, Daniel J Wilke, Riva A Desai, Andrew J Loza, Peinan Zhao, Anne Lohrey, Gregory D Longmore, Katherine C Fuh
The mesenchymal gene program has been shown to promote the metastatic progression of ovarian cancer; however, specific proteins induced by this program that lead to these metastatic behaviors have not been identified. Using patient derived tumor cells and established human ovarian tumor cell lines, we find that the Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that recognizes fibrillar collagen as ligand...
January 19, 2018: Oncogene
Haruta Mogami, Annavarapu Hari Kishore, R Ann Word
Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth. Recently, extracellular matrix-directed treatment is applied for wound healing. Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel for healing of the prematurely ruptured fetal membranes. Although injection of PBS into the ruptured fetal membranes resulted in 40% closure, injection of collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2 wound healing phenotype were entrapped in the collagen layer...
January 12, 2018: Scientific Reports
Maria Rosaria Raspollini, Ilaria Montagnani, Rodolfo Montironi, Francesca Castiglione, Guido Martignoni, Liang Cheng, Antonio Lopez-Beltran
Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status...
January 9, 2018: Journal of Clinical Pathology
Jung Ran Choi, Sang-Baek Koh, Seong Yong Park, Hye Run Kim, Hyojin Lee, Dae Ryong Kang
Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs...
December 2017: Journal of Cancer Prevention
Zhong Liang, Wen-Jun Xie, Ming Zhao, Guo-Ping Cheng, Mei-Juan Wu
The upregulation of discoidin domain receptor tyrosine kinase 2 (DDR2) has been reported to be associated with poor prognosis and metastasis in numerous tumor types by inducing epithelial-mesenchymal transition (EMT); however, the expression profile of DDR2 in papillary thyroid carcinoma (PTC) with local metastasis and the effect of DDR2 on PTC cells remain unknown. The aim of the present study was to investigate the expression levels of DDR2 in tumor tissues of patients with PTC with local metastasis and cell lines and to determine the effect of DDR2 on EMT in PTC cells...
December 2017: Oncology Letters
Keran Jiang, Zhongli Yang, Wenyan Cui, Kunkai Su, Jennie Z Ma, Thomas J Payne, Ming D Li
Introduction: Cigarette smoking is one of the largest causes of preventable death worldwide. This study aimed to identify susceptibility loci for age at smoking initiation (ASI) by performing exome-wide association analysis. Methods: A total of 2,510 smokers of either African-American (AA) or European-American (EA) origin were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and gene levels. After removal of those SNPs with minor allele frequency (<0...
December 5, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Thi Y L Le, Hilda A Pickett, Cristobal G Dos Remedios, Pasquale M Barbaro, Eddy Kizana, James J H Chong
Cardiac progenitor cells (CPCs) are being developed as a promising treatment for heart failure. Although clinical trials have predominantly used donor cardiac biopsies to derive CPCs, a better solution could be to use previously cryopreserved human heart tissue. This would enable timely and convenient access to healthy and young heart samples for CPC production. However, few studies have attempted to isolate CPCs from previously cryopreserved heart tissue. In this study, we isolated CPCs from eight nondiseased human heart samples previously cryopreserved as part of the Sydney Heart Bank...
February 1, 2018: Stem Cells and Development
T Puri
Activating mutations in the epidermal growth factor receptor gene and rearrangement of the anaplastic lymphoma kinase gene exemplify the molecular characterization of nonsmall cell lung cancer (NSCLC), particularly adenocarcinoma, and its therapeutic relevance. Several genetic alterations with prognostic and predictive role, including ROS, RET, MET, KRAS, have now been identified in adenocarcinoma and some such as DDR2 and fibroblast growth factor receptor 1 in squamous cell carcinoma. This has heralded the development of agents targeted against these aberrations...
January 2017: Indian Journal of Cancer
Charles Ricordel, Alexandra Lespagnol, Francisco Llamas-Gutierrez, Marie de Tayrac, Mallorie Kerjouan, Alice Fievet, Houda Hamdi-Rozé, Amyrat Aliouat, Benoit Desrues, Jean Mosser, Hervé Léna
BACKGROUND: Lung cancer represents the leading cause of cancer-related death worldwide. Despite great advances in lung cancer management with the recent emergence of molecular targeted therapies for non-squamous non-small-cell lung cancer, no dramatic improvements have been achieved in lung squamous cell carcinoma (SCC). Mutations in discoidin domain receptor 2 (DDR2) gene were recently identified as promising molecular targets in this histology. The aim of this study is to describe the DDR2 mutational landscape of lung SCC and investigate the associated clinical factors...
October 19, 2017: Clinical Lung Cancer
Christian Klopsch, Anna Skorska, Marion Ludwig, Ralf Gaebel, Heiko Lemcke, Gabriela Kleiner, Martin Beyer, Brigitte Vollmar, Robert David, Gustav Steinhoff
BACKGROUND/PURPOSE: Cardiac mesenchymal stem cells (MSCs) could stimulate cell-specific regenerative mechanisms after myocardial infarction (MI) depending on spatial origin, distribution, and niche regulation. We aimed at identifying and isolating tissue-specific cardiac MSCs that could contribute to regeneration. METHODS: Following permanent ligation of the left anterior descending coronary artery in rats (n = 16), early cardiac tissues and cardiac mononuclear cells (MNCs) were analyzed by immunohistology, confocal laser scanning microscopy, and flow cytometry, respectively...
October 26, 2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
C Ge, F Mohamed, A Binrayes, S Kapila, R T Franceschi
Temporomandibular joint (TMJ) disorders are often associated with development of osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor 2 (DDR2), a collagen receptor preferentially activated by type I and III collagen found in the TMJ and other fibrocartilages, has been associated with TMJ degeneration, but its role in normal joint development has not been previously examined. Using Ddr2 LacZ-tagged mice and immunohistochemistry, we found that DDR2 is preferentially expressed and activated in the articular zone of TMJs but not knee joints...
October 1, 2017: Journal of Dental Research
Daiqiang Li, Zhulin Yang, Ziru Liu, Qiong Zou, Yuan Yuan
This study was conducted to investigate the expressions of DDR2 and IFITM1 and their clinical and pathological significances in the rare type squamous cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and 146 ACs using EnVision immunohistochemistry. Results showed that the percentage of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC patients with high TNM stage, lymph node metastasis, invasion, and no resection surgery compared to patients with low TNM stages, no lymph node metastasis, no invasion, and resection surgery (P < 0...
October 17, 2017: Pathology Oncology Research: POR
Ming-Tao Zhao, Ning-Yi Shao, Shijun Hu, Ning Ma, Rajini Srinivasan, Fereshteh Jahanbani, Jaecheol Lee, Sophia L Zhang, Michael P Snyder, Joseph C Wu
RATIONALE: Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. OBJECTIVE: We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression...
November 10, 2017: Circulation Research
Nadza Tokaca, Sarah Barth, Mary O'Brien, Jaishree Bhosle, Nicos Fotiadis, Andrew Wotherspoon, Lisa Thompson, Sanjay Popat
INTRODUCTION: In the era of biomarker-driven systemic therapy for advanced NSCLC, the role of routine repeated biopsies for decision making outside EGFR-mutant disease remains unproven. We report our center's experience of safety and adequacy for molecular retesting of tumor material obtained from image-guided lung rebiopsies in NSCLC. METHODS: We performed a retrospective case note analysis of patients undergoing image-guided lung rebiopsies at a single cancer center between 2011 and 2014...
January 2018: Journal of Thoracic Oncology
Hesham Mostafa, Bruno Pedroni, Sadique Sheik, Gert Cauwenberghs
Artificial neural networks (ANNs) trained using backpropagation are powerful learning architectures that have achieved state-of-the-art performance in various benchmarks. Significant effort has been devoted to developing custom silicon devices to accelerate inference in ANNs. Accelerating the training phase, however, has attracted relatively little attention. In this paper, we describe a hardware-efficient on-line learning technique for feedforward multi-layer ANNs that is based on pipelined backpropagation...
2017: Frontiers in Neuroscience
Michaeline Hebron, Margo Peyton, Xiaoguang Liu, Xiaokong Gao, Ruochong Wang, Irina Lonskaya, Charbel E-H Moussa
The role of cell surface tyrosine kinase collagen-activated receptors known as discoidin domain receptors (DDRs) is unknown in neurodegenerative diseases. We detect up-regulation in DDRs level in post-mortem Alzheimer and Parkinson brains. Lentiviral shRNA knockdown of DDR1 and DDR2 reduces the levels of α-synuclein, tau, and β-amyloid and prevents cell loss in vivo and in vitro. DDR1 and DDR2 knockdown alters brain immunity and significantly reduces the level of triggering receptor expressed on myeloid cells (TREM)-2 and microglia...
October 15, 2017: Journal of Neuroimmunology
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