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https://www.readbyqxmd.com/read/28270508/discoidin-domain-receptor-2-mediates-collagen-induced-activation-of-membrane-type-1-matrix-metalloproteinase-in-human-fibroblasts
#1
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 cell. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it upregulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation is not clearly understood. In this study we identified discoidin domain receptor 2 (DDR2) as a crucial receptor that mediates this process in human fibroblasts...
March 7, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27398168/prognostic-significance-of-discoidin-domain-receptor-2-ddr2-expression-in-ovarian-cancer
#13
Yi Fan, Zhe Xu, Jin Fan, Liu Huang, Ming Ye, Kun Shi, Zheng Huang, Yaqiong Liu, Langchi He, Jiezhen Huang, Yibin Wang, Qiufeng Li
Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27350126/targeting-of-discoidin-domain-receptor-2-ddr2-prevents-myofibroblast-activation-and-neovessel-formation-during-pulmonary-fibrosis
#14
Hu Zhao, Huan Bian, Xin Bu, Shuya Zhang, Pan Zhang, Jiangtian Yu, Xiaofeng Lai, Di Li, Chuchao Zhu, Libo Yao, Jin Su
Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression...
October 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27341689/discoidin-receptor-2-controls-bone-formation-and-marrow-adipogenesis
#15
Chunxi Ge, Zhengyan Wang, Guisheng Zhao, Binbin Li, Jinhui Liao, Hanshi Sun, Renny T Franceschi
Cell-extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), is an important mediator of interactions between cells and fibrillar collagens. DDR2 signals through both ERK1/2 and p38 MAP kinase, which stimulate osteoblast differentiation and bone formation. Here we show that DDR2 is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis...
December 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27322034/multiple-directional-differentiation-difference-of-neonatal-rat-fibroblasts-from-six-organs
#16
Yuqiao Chang, Kang Guo, Qiong Li, Cixia Li, Zhikun Guo, He Li
BACKGROUND/AIMS: Fibroblasts are abundantly distributed throughout connective tissues in the body and are very important in maintaining the structural and functional integrity. Recent reports have proved that fibroblasts and mesenchymal stem cells share much more in common than previously recognized. The aim of this study was to investigate comparative studies in fibroblasts on the differences in the expression of molecular markers and differentiation capacity from different organs. METHODS: Combined trypsin/collagenase enzymes digestion method was used to isolate and culture the fibroblasts derived from heart, liver, spleen, lung, kidney and skin...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27264173/the-action-of-discoidin-domain-receptor-2-in-basal-tumor-cells-and-stromal-cancer-associated-fibroblasts-is-critical-for-breast-cancer-metastasis
#17
Callie A S Corsa, Audrey Brenot, Whitney R Grither, Samantha Van Hove, Andrew J Loza, Kun Zhang, Suzanne M Ponik, Yuming Liu, David G DeNardo, Kevin W Eliceiri, Patricia J Keely, Gregory D Longmore
High levels of collagen deposition in human and mouse breast tumors are associated with poor outcome due to increased local invasion and distant metastases. Using a genetic approach, we show that, in mice, the action of the fibrillar collagen receptor discoidin domain receptor 2 (DDR2) in both tumor and tumor-stromal cells is critical for breast cancer metastasis yet does not affect primary tumor growth. In tumor cells, DDR2 in basal epithelial cells regulates the collective invasion of tumor organoids. In stromal cancer-associated fibroblasts (CAFs), DDR2 is critical for extracellular matrix production and the organization of collagen fibers...
June 14, 2016: Cell Reports
https://www.readbyqxmd.com/read/27121621/cardiac-fibro-adipocyte-progenitors-express-desmosome-proteins-and-preferentially-differentiate-to-adipocytes-upon-deletion-of-the-desmoplakin-gene
#18
Raffaella Lombardi, Suet Nee Chen, Alessandra Ruggiero, Priyatansh Gurha, Grazyna Z Czernuszewicz, James T Willerson, Ali J Marian
RATIONALE: Mutations in desmosome proteins cause arrhythmogenic cardiomyopathy (AC), a disease characterized by excess myocardial fibroadipocytes. Cellular origin(s) of fibroadipocytes in AC is unknown. OBJECTIVE: To identify the cellular origin of adipocytes in AC. METHODS AND RESULTS: Human and mouse cardiac cells were depleted from myocytes and flow sorted to isolate cells expressing platelet-derived growth factor receptor-α and exclude those expressing other lineage and fibroblast markers (CD32, CD11B, CD45, Lys76, Ly(-6c) and Ly(6c), thymocyte differentiation antigen 1, and discoidin domain receptor 2)...
June 24, 2016: Circulation Research
https://www.readbyqxmd.com/read/27121209/targeted-sequencing-identifies-genetic-alterations-that-confer-primary-resistance-to-egfr-tyrosine-kinase-inhibitor-korean-lung-cancer-consortium
#19
Sun Min Lim, Hye Ryun Kim, Eun Kyung Cho, Young Joo Min, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Byoung Chul Cho, Ji-Hyun Lee, Hye Cheol Jeong, Eun Kyung Kim, Joo-Hang Kim
BACKGROUND: Non-small-cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations may exhibit primary resistance to EGFR tyrosine kinase inhibitor (TKI). We aimed to examine genomic alterations associated with de novo resistance to gefitinib in a prospective study of NSCLC patients. Patients and methods: One-hundred and fifty two patients with activating EGFR mutations were included in this study and 136 patients' tumor sample were available for targeted sequencing of genomic alterations in 22 genes using the Colon and Lung Cancer panel (Ampliseq, Life Technologies)...
June 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27121132/type-i-collagen-aging-impairs-discoidin-domain-receptor-2-mediated-tumor-cell-growth-suppression
#20
Charles Saby, Emilie Buache, Sylvie Brassart-Pasco, Hassan El Btaouri, Marie-Pierre Courageot, Laurence Van Gulick, Roselyne Garnotel, Pierre Jeannesson, Hamid Morjani
Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2...
May 3, 2016: Oncotarget
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