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https://www.readbyqxmd.com/read/28743124/the-role-of-discoidin-domain-receptor-1-in-inflammation-fibrosis-and-renal-disease
#1
Aude Dorison, Jean-Claude Dussaule, Christos Chatziantoniou
Discoidin domain receptors (DDRs) are a family of 2 non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. They are mainly expressed during embryonic development and their role during adulthood is very limited. DDR1 has been widely studied in several types of cancers, in atherosclerosis and fibrosis, but also in chronic kidney disease (CKD). This review focuses on the role of DDR1 in chronic nephropathies and on the effect of its deletion in the pathological processes involved in renal disease progression...
July 26, 2017: Nephron
https://www.readbyqxmd.com/read/28714692/design-synthesis-and-pharmacological-evaluation-of-novel-multisubstituted-pyridin-3-amine-derivatives-as-multitargeted-protein-kinase-inhibitors-for-the-treatment-of-non-small-cell-lung-cancer
#2
Wei Zhu, Hui Chen, Yulan Wang, Jiang Wang, Xia Peng, Xianjie Chen, Yinglei Gao, Chunpu Li, Yulong He, Jing Ai, Meiyu Geng, Mingyue Zheng, Hong Liu
A novel series of pyridin-3-amine derivatives were designed, synthesized, and evaluated as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC). Hit 1 was first disclosed by in silico screening against fibroblast growth factor receptors (FGFR), which was subsequently validated by in vitro experiments. The structure-activity relationship (SAR) of its analogues was then explored to afford novel FGFR inhibitors 2a-2p and 3a-3q. Among them, 3m showed potent inhibition against FGFR1, 2, and 3...
July 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28700752/role-of-a-novel-immune-modulating-ddr2-expressing-population-in-silica-induced-pulmonary-fibrosis
#3
Lindsay T McDonald, Sara D Johnson, Dayvia L Russell, M Rita I Young, Amanda C LaRue
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28676216/functional-analysis-of-discoidin-domain-receptor-2-mutation-and-expression-in-squamous-cell-lung-cancer
#4
Naomi Kobayashi-Watanabe, Akemi Sato, Tatsuro Watanabe, Tomonori Abe, Chiho Nakashima, Eisaburo Sueoka, Shinya Kimura, Naoko Sueoka-Aragane
OBJECTIVES: Discoidin domain receptor (DDR) 2 mutations have recently been reported to be candidate targets of molecular therapy in lung squamous cell carcinoma (SQCC). However, the status of DDR2 expression and mutations, as well as their precise roles in lung SQCC, have not been clarified. We here report DDR2 mutation and expression status in clinical samples and its role of lung SQCC. MATERIALS AND METHODS: We investigated DDR2 expression and mutation status in 44 human clinical samples and 7 cell lines...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28619094/morphologic-and-molecular-study-of-lung-cancers-associated-with-idiopathic-pulmonary-fibrosis-and-other-pulmonary-fibroses
#5
Alice Guyard, Claire Danel, Nathalie Théou-Anton, Marie-Pierre Debray, Laure Gibault, Pierre Mordant, Yves Castier, Bruno Crestani, Gérard Zalcman, Hélène Blons, Aurélie Cazes
BACKGROUND: Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). METHODS: Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28606737/long-term-survival-in-a-patient-with-metastatic-ddr2-positive-adrenal-cortical-carcinoma
#6
Fadi Taza, Michal Chovanec, Noah Hahn, Costantine Albany
No abstract text is available yet for this article.
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28590426/down-s-syndrome-and-triple-negative-breast-cancer-a-rare-occurrence-of-distinctive-clinical-relationship
#7
Nandini Dey, Amy Krie, Jessica Klein, Kirstin Williams, Amanda McMillan, Rachel Elsey, Yuliang Sun, Casey Williams, Pradip De, Brian Leyland-Jones
Down's syndrome (DS), the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21). Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28446466/landscape-of-combination-immunotherapy-and-targeted-therapy-to-improve-cancer-management
#8
Leandro M Colli, Mitchell J Machiela, Han Zhang, Timothy A Myers, Lea Jessop, Olivier Delattre, Kai Yu, Stephen J Chanock
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic datasets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide nonsynonymous mutations (NsM) that exceed a proposed threshold for response to checkpoint inhibitors...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28270508/discoidin-domain-receptor-2-mediates-collagen-induced-activation-of-membrane-type-1-matrix-metalloproteinase-in-human-fibroblasts
#9
Iwona Majkowska, Yasuyuki Shitomi, Noriko Ito, Nathanael S Gray, Yoshifumi Itoh
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity, including fibroblasts and invasive cancer cells. However, pathways of MT1-MMP up-regulation are not clearly understood. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it up-regulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation and its physiological relevance are not known...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#10
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28161936/prevalence-of-mutations-in-discoidin-domain-containing-receptor-tyrosine-kinase-2-ddr2-in-squamous-cell-lung-cancers-in-korean-patients
#11
Mi-Sook Lee, Eun Ah Jung, Sung Bin An, Yu Jin Kim, Doo-Yi Oh, Ji-Young Song, Sang-Won Um, Joungho Han, Yoon-La Choi
Purpose: The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer. Materials and Methods: We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination...
January 25, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28147276/mesenchymal-stem-cell-induced-ddr2-mediates-stromal-breast-cancer-interactions-and-metastasis-growth
#12
Maria E Gonzalez, Emily E Martin, Talha Anwar, Caroline Arellano-Garcia, Natasha Medhora, Arjun Lama, Yu-Chih Chen, Kevin S Tanager, Euisik Yoon, Kelley M Kidwell, Chunxi Ge, Renny T Franceschi, Celina G Kleer
Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28097440/prevalence-of-nras-pten-and-akt1-gene-mutations-in-the-central-nervous-system-metastases-of-non-small-cell-lung-cancer
#13
Marcin Nicoś, Paweł Krawczyk, Bożena Jarosz, Marek Sawicki, Tomasz Trojanowski, Janusz Milanowski
Somatic mutations in NRAS, PTEN and AKT1 genes are rarely (~1%) reported in primary NSCLC, but their role in carcinogenesis have been proven. Therefore, we assessed the frequency of them in 145 FFPE tissue samples from CNS metastases of NSCLC using the real-time PCR technique. We identified four (two NRAS and single AKT1 and PTEN) mutations in CNS metastases of NSCLC. All mutations were observed in current male smokers (4% out of the male group; 4/100 and 4.25% out of smokers; 4/94). Three mutations have been detected in patients with SqCC (10...
January 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/27793038/ddr2-overexpression-in-urothelial-carcinoma-indicates-an-unfavorable-prognosis-a-large-cohort-study
#14
Meng-Chen Tsai, Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Ti-Chun Chan, Peir-In Liang, Bi-Wen Yeh, Wen-Jeng Wu, Sher-Wei Lim, Chien-Feng Li
The migration ability of urothelial carcinoma corresponding to dismal prognosis had not been fully investigated. The interaction of extracellular collagen with a unique transmembrane receptor tyrosine kinase, Discoidin domain receptor 2 (DDR2), was selected by data mining. We arranged real-time reverse transcription polymerase chain reaction assays to evaluate the transcript levels in 26 urinary tract urothelial carcinoma and 26 urinary bladder urothelial carcinoma specimens, showing significantly increase corresponding to advanced primary stage (p = 0...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27640147/discoidin-domain-receptor-2-as-a-potential-therapeutic-target-for-development-of-disease-modifying-osteoarthritis-drugs
#15
Lauren B Manning, Yefu Li, Nithya S Chickmagalur, Xiaolong Li, Lin Xu
Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints. Aggrecan-CreERT2;floxed Ddr2 mice, which were generated by crossing Aggrecan-CreERT2 mice with floxed Ddr2 mice, then received tamoxifen injections at the age of 8 weeks...
September 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27639803/cell-culture-system-for-analysis-of-genetic-heterogeneity-within%C3%A2-hepatocellular-carcinomas-and-response-to-pharmacologic-agents
#16
Qiang Gao, Zhi-Chao Wang, Meng Duan, Yi-Hui Lin, Xue-Ya Zhou, Daniel L Worthley, Xiao-Ying Wang, Gang Niu, Yuchao Xia, Minghua Deng, Long-Zi Liu, Jie-Yi Shi, Liu-Xiao Yang, Shu Zhang, Zhen-Bin Ding, Jian Zhou, Chun-Min Liang, Ya Cao, Lei Xiong, Ruibin Xi, Yong-Yong Shi, Jia Fan
BACKGROUND & AIMS: No targeted therapies have been found to be effective against hepatocellular carcinoma (HCC), possibly due to the large degree of intratumor heterogeneity. We performed genetic analyses of different regions of HCCs to evaluate levels of intratumor heterogeneity and associate alterations with responses to different pharmacologic agents. METHODS: We obtained samples of HCCs (associated with hepatitis B virus infection) from 10 patients undergoing curative resection, before adjuvant therapy, at hospitals in China...
January 2017: Gastroenterology
https://www.readbyqxmd.com/read/27589335/synthesis-and-biological-evaluation-of-novel-dasatinib-analogues-as-potent-ddr1-and-ddr2-kinase-inhibitors
#17
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...
March 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27546376/transcriptional-targets-of-twist1-in-the-cranial-mesoderm-regulate-cell-matrix-interactions-and-mesenchyme-maintenance
#18
Heidi Bildsoe, Xiaochen Fan, Emilie E Wilkie, Ator Ashoti, Vanessa J Jones, Melinda Power, Jing Qin, Junwen Wang, Patrick P L Tam, David A F Loebel
TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. We have previously shown that, in the absence of TWIST1, cells within the cranial mesoderm adopt an abnormal epithelial configuration via a process reminiscent of a mesenchymal to epithelial transition (MET). Here, we show by gene expression analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics...
October 1, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27475236/an-integrative-approach-predicted-co-expression-sub-networks-regulating-properties-of-stem-cells-and-differentiation
#19
Mousumi Sahu, Bibekanand Mallick
The differentiation of human Embryonic Stem Cells (hESCs) is accompanied by the formation of different intermediary cells, gradually losing its stemness and acquiring differentiation. The precise mechanisms underlying hESCs integrity and its differentiation into fibroblast (Fib) are still elusive. Here, we aimed to assess important genes and co-expression sub-networks responsible for stemness, early differentiation of hESCs into embryoid bodies (EBs) and its lineage specification into Fibs. To achieve this, we compared transcriptional profiles of hESCs-EBs and EBs-Fibs and obtained differentially expressed genes (DEGs) exclusive to hESCs-EBs (early differentiation), EBs-Fibs (late differentiation) and common DEGs in hESCs-EBs and EBs-Fibs...
October 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27434411/targeting-ddr2-in-head-and-neck-squamous-cell-carcinoma-with-dasatinib
#20
Anne von Mässenhausen, Christine Sanders, Johannes Brägelmann, Martina Konantz, Angela Queisser, Wenzel Vogel, Glen Kristiansen, Stefan Duensing, Andreas Schröck, Friedrich Bootz, Peter Brossart, Jutta Kirfel, Claudia Lengerke, Sven Perner
Squamous cell carcinoma of the head and neck (HNSCC) is the tenth most common tumor entity in men worldwide. Nevertheless therapeutic options are mostly limited to surgery and radio-chemotherapy resulting in 5-year survival rates of around 50%. Therefore new therapeutic options are urgently needed. During the last years, targeting of receptor tyrosine kinases has emerged as a promising strategy that can complement standard therapeutical approaches. Here, we aimed at investigating if the receptor tyrosine kinase DDR2 is a targetable structure in HNSCC...
November 15, 2016: International Journal of Cancer. Journal International du Cancer
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