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  1. Article ; Online: Concepts of extracellular matrix remodelling in tumour progression and metastasis

    Juliane Winkler / Abisola Abisoye-Ogunniyan / Kevin J. Metcalf / Zena Werb

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 19

    Abstract: Tumors are more than cancer cells — the extracellular matrix is a protein structure that organizes all tissues and is altered in cancer. Here, the authors review recent progress in understanding how the cancer cells and tumor-associated stroma cells ... ...

    Abstract Tumors are more than cancer cells — the extracellular matrix is a protein structure that organizes all tissues and is altered in cancer. Here, the authors review recent progress in understanding how the cancer cells and tumor-associated stroma cells remodel the extracellular matrix to drive tumor growth and metastasis.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Concepts of extracellular matrix remodelling in tumour progression and metastasis

    Juliane Winkler / Abisola Abisoye-Ogunniyan / Kevin J. Metcalf / Zena Werb

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 19

    Abstract: Tumors are more than cancer cells — the extracellular matrix is a protein structure that organizes all tissues and is altered in cancer. Here, the authors review recent progress in understanding how the cancer cells and tumor-associated stroma cells ... ...

    Abstract Tumors are more than cancer cells — the extracellular matrix is a protein structure that organizes all tissues and is altered in cancer. Here, the authors review recent progress in understanding how the cancer cells and tumor-associated stroma cells remodel the extracellular matrix to drive tumor growth and metastasis.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Circulating Tumor Cells

    Plaks, Vicki / Charlotte D. Koopman / Zena Werb

    Science. 2013 Sept. 13, v. 341, no. 6151

    2013  

    Abstract: The major cause of cancer-associated mortality is tumor metastasis, but our understanding of this process is far from complete. During successful dissemination, tumor cells invade the surrounding tissue of the primary tumor, intravasate into blood and ... ...

    Abstract The major cause of cancer-associated mortality is tumor metastasis, but our understanding of this process is far from complete. During successful dissemination, tumor cells invade the surrounding tissue of the primary tumor, intravasate into blood and lymphatic vessels, translocate to distant tissues, extravasate, adapt to the new microenvironment, and eventually seed, proliferate, and colonize to form metastases. Because dissemination mostly occurs through the blood, circulating tumor cells (CTCs) that have been shed into the vasculature and may be on their way to potential metastatic sites are of obvious interest (1). Here we discuss what is known about CTCs, and suggest future research directions that may help realize their clinical potential.
    Keywords blood ; metastasis ; mortality ; neoplasm cells
    Language English
    Dates of publication 2013-0913
    Size p. 1186-1188.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1235226
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  4. Article: Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity

    Lemieux, George A / Katherine A. Cunningham / Lin Lin / Fahima Mayer / Zena Werb / Kaveh Ashrafi

    Cell. 2015 Jan. 15, v. 160

    2015  

    Abstract: The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases, but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food- ... ...

    Abstract The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases, but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food-dependent behavioral plasticity in C. elegans. The experience of fasting in C. elegans alters a variety of behaviors, including feeding rate, when food is encountered post-fast. Levels of neurally produced kynurenic acid are depleted by fasting, leading to activation of NMDA-receptor-expressing interneurons and initiation of a neuropeptide-y-like signaling axis that promotes elevated feeding through enhanced serotonin release when animals re-encounter food. Upon refeeding, kynurenic acid levels are eventually replenished, ending the elevated feeding period. Because tryptophan is an essential amino acid, these findings suggest that a physiological role of kynurenic acid is in directly linking metabolism to activity of NMDA and serotonergic circuits, which regulate a broad range of behaviors and physiologies.
    Keywords animals ; central nervous system diseases ; essential amino acids ; fasting ; interneurons ; kynurenine pathway ; metabolism ; metabolites ; pathogenesis ; refeeding ; serotonin ; tryptophan
    Language English
    Dates of publication 2015-0115
    Size p. 119-131.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2014.12.028
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 75/702: Show issues
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  5. Article ; Online: Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity

    Quy H. Nguyen / Nicholas Pervolarakis / Kerrigan Blake / Dennis Ma / Ryan Tevia Davis / Nathan James / Anh T. Phung / Elizabeth Willey / Raj Kumar / Eric Jabart / Ian Driver / Jason Rock / Andrei Goga / Seema A. Khan / Devon A. Lawson / Zena Werb / Kai Kessenbrock

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 12

    Abstract: Epithelial subpopulations are present in the human breast but how these differentiate or form is unclear. Here, the authors use single-cell RNA sequencing of primary human breast epithelial cells to define previously undescribed luminal, basal epithelial ...

    Abstract Epithelial subpopulations are present in the human breast but how these differentiate or form is unclear. Here, the authors use single-cell RNA sequencing of primary human breast epithelial cells to define previously undescribed luminal, basal epithelial subpopulations and ZEB1-positive basal cells.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity

    Quy H. Nguyen / Nicholas Pervolarakis / Kerrigan Blake / Dennis Ma / Ryan Tevia Davis / Nathan James / Anh T. Phung / Elizabeth Willey / Raj Kumar / Eric Jabart / Ian Driver / Jason Rock / Andrei Goga / Seema A. Khan / Devon A. Lawson / Zena Werb / Kai Kessenbrock

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 12

    Abstract: Epithelial subpopulations are present in the human breast but how these differentiate or form is unclear. Here, the authors use single-cell RNA sequencing of primary human breast epithelial cells to define previously undescribed luminal, basal epithelial ...

    Abstract Epithelial subpopulations are present in the human breast but how these differentiate or form is unclear. Here, the authors use single-cell RNA sequencing of primary human breast epithelial cells to define previously undescribed luminal, basal epithelial subpopulations and ZEB1-positive basal cells.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Impaired remodeling phase of fracture repair in the absence of matrix metalloproteinase-2

    Shirley Lieu / Erik Hansen / Russell Dedini / Danielle Behonick / Zena Werb / Theodore Miclau / Ralph Marcucio / Céline Colnot

    Disease Models & Mechanisms, Vol 4, Iss 2, Pp 203-

    2011  Volume 211

    Abstract: SUMMARY The matrix metalloproteinase (MMP) family of extracellular proteases performs crucial roles in development and repair of the skeleton owing to their ability to remodel the extracellular matrix (ECM) and release bioactive molecules. Most MMP-null ... ...

    Abstract SUMMARY The matrix metalloproteinase (MMP) family of extracellular proteases performs crucial roles in development and repair of the skeleton owing to their ability to remodel the extracellular matrix (ECM) and release bioactive molecules. Most MMP-null skeletal phenotypes that have been previously described are mild, thus permitting the assessment of their functions during bone repair in the adult. In humans and mice, MMP2 deficiency causes a musculoskeletal phenotype. In this study, we assessed the role of MMP2 during mouse fracture repair and compared it with the roles of MMP9 and MMP13. Mmp2 was expressed at low levels in the normal skeleton and was broadly expressed in the fracture callus. Treatment of wild-type mice with a general MMP inhibitor, GM6001, caused delayed cartilage remodeling and bone formation during fracture repair, which resembles the defect observed in Mmp9–/– mice. Unlike Mmp9- and Mmp13-null mutations, which affect both cartilage and bone in the callus, the Mmp2-null mutation delayed bone remodeling but not cartilage remodeling. This remodeling defect occurred without changes in either osteoclast recruitment or vascular invasion of the fracture callus compared with wild type. However, we did not detect changes in expression of Mmp9, Mmp13 or Mt1-Mmp (Mmp14) in the calluses of Mmp2-null mice compared with wild type by in situ hybridization, but we observed decreased expression of Timp2 in the calluses of Mmp2-, Mmp9- and Mmp13-null mice. In keeping with the skeletal phenotype of Mmp2-null mice, MMP2 plays a role in the remodeling of new bone within the fracture callus and impacts later stages of bone repair compared with MMP9 and MMP13. Taken together, our results indicate that MMPs play unique and distinct roles in regulating skeletal tissue deposition and remodeling during fracture repair.
    Keywords Medicine ; R ; Pathology ; RB1-214
    Subject code 616
    Language English
    Publishing date 2011-03-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers

    Roni Allaoui / Caroline Bergenfelz / Sofie Mohlin / Catharina Hagerling / Kiarash Salari / Zena Werb / Robin L. Anderson / Stephen P. Ethier / Karin Jirström / Sven Påhlman / Daniel Bexell / Balázs Tahin / Martin E. Johansson / Christer Larsson / Karin Leandersson

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Volume 14

    Abstract: A reactive tumour stroma is associated with poor prognosis. Here, the authors show that in patients with triple negative breast cancer resident monocytes activate cancer-associated fibroblasts and induce production of CXCL16, which acts as a monocyte ... ...

    Abstract A reactive tumour stroma is associated with poor prognosis. Here, the authors show that in patients with triple negative breast cancer resident monocytes activate cancer-associated fibroblasts and induce production of CXCL16, which acts as a monocyte chemoattractant, resulting in an amplificatory feedback loop.
    Keywords Science ; Q
    Language English
    Publishing date 2016-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Efficacy of a metalloproteinase inhibitor in spinal cord injured dogs.

    Jonathan M Levine / Noah D Cohen / Michael Heller / Virginia R Fajt / Gwendolyn J Levine / Sharon C Kerwin / Alpa A Trivedi / Thomas M Fandel / Zena Werb / Augusta Modestino / Linda J Noble-Haeusslein

    PLoS ONE, Vol 9, Iss 5, p e

    2014  Volume 96408

    Abstract: Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. ... ...

    Abstract Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic events that emerge in the acutely injured ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Endovascular biopsy: Strategy for analyzing gene expression profiles of individual endothelial cells obtained from human vessels

    Sun, Zhengda / Chih-Yang Wang / Christopher F. Dowd / Daniel L. Cooke / Devon A. Lawson / Elizabeth Sinclair / Hua Su / Ming-Derg Lai / Randall T. Higashida / Steven W. Hetts / Van V. Halbach / Zena Werb

    Biotechnology reports. 2015 Sept., v. 7

    2015  

    Abstract: To develop a strategy of achieving targeted collection of endothelial cells (ECs) by endovascular methods and analyzing the gene expression profiles of collected single ECs.134 ECs and 37 leukocytes were collected from four patients' intra-iliac artery ... ...

    Abstract To develop a strategy of achieving targeted collection of endothelial cells (ECs) by endovascular methods and analyzing the gene expression profiles of collected single ECs.134 ECs and 37 leukocytes were collected from four patients' intra-iliac artery endovascular guide wires by fluorescence activated cell sorting (FACS) and analyzed by single-cell quantitative RT-PCR for expression profile of 48 genes. Compared to CD45+ leukocytes, the ECs expressed higher levels (p<0.05) of EC surface markers used on FACS and other EC related genes. The gene expression profile showed that these isolated ECs fell into two clusters, A and B, that differentially expressed 19 genes related to angiogenesis, inflammation and extracellular matrix remodeling, with cluster B ECs have demonstrating similarities to senescent or aging ECs.Combination of endovascular device sampling, FACS and single-cell quantitative RT-PCR is a feasible method for analyzing EC gene expression profile in vascular lesions.
    Keywords angiogenesis ; biopsy ; biotechnology ; endothelial cells ; extracellular matrix ; flow cytometry ; gene expression ; gene expression regulation ; genes ; humans ; inflammation ; leukocytes ; patients ; reverse transcriptase polymerase chain reaction
    Language English
    Dates of publication 2015-09
    Size p. 157-165.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2801018-8
    ISSN 2215-017X
    ISSN 2215-017X
    DOI 10.1016/j.btre.2015.07.001
    Database NAL-Catalogue (AGRICOLA)

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