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  • 1
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    CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-09-17
    Description: Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex, is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587138/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587138/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Firestein, Ron -- Bass, Adam J -- Kim, So Young -- Dunn, Ian F -- Silver, Serena J -- Guney, Isil -- Freed, Ellen -- Ligon, Azra H -- Vena, Natalie -- Ogino, Shuji -- Chheda, Milan G -- Tamayo, Pablo -- Finn, Stephen -- Shrestha, Yashaswi -- Boehm, Jesse S -- Jain, Supriya -- Bojarski, Emeric -- Mermel, Craig -- Barretina, Jordi -- Chan, Jennifer A -- Baselga, Jose -- Tabernero, Josep -- Root, David E -- Fuchs, Charles S -- Loda, Massimo -- Shivdasani, Ramesh A -- Meyerson, Matthew -- Hahn, William C -- K08 CA134931/CA/NCI NIH HHS/ -- P50CA127003/CA/NCI NIH HHS/ -- R33 CA128625/CA/NCI NIH HHS/ -- R33 CA128625-01A1/CA/NCI NIH HHS/ -- R33CA128625/CA/NCI NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Sep 25;455(7212):547-51. doi: 10.1038/nature07179. Epub 2008 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18794900" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Colorectal Neoplasms/*genetics/*metabolism/pathology ; Cyclin-Dependent Kinase 8 ; Cyclin-Dependent Kinases/deficiency/*genetics/*metabolism ; Gene Dosage ; *Gene Expression Regulation, Neoplastic ; Humans ; Oncogene Proteins/deficiency/genetics/metabolism ; *Oncogenes ; RNA Interference ; Transcription, Genetic ; beta Catenin/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Restriction of intestinal stem cell expansion and the regenerative response by YAP (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-11-28
    Description: A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate in mice and humans that yes-associated protein 1 (YAP; also known as YAP1)--a protein known for its powerful growth-inducing and oncogenic properties--has an unexpected growth-suppressive function, restricting Wnt signals during intestinal regeneration. Transgenic expression of YAP reduces Wnt target gene expression and results in the rapid loss of intestinal crypts. In addition, loss of YAP results in Wnt hypersensitivity during regeneration, leading to hyperplasia, expansion of intestinal stem cells and niche cells, and formation of ectopic crypts and microadenomas. We find that cytoplasmic YAP restricts elevated Wnt signalling independently of the AXIN-APC-GSK-3beta complex partly by limiting the activity of dishevelled (DVL). DVL signals in the nucleus of intestinal stem cells, and its forced expression leads to enhanced Wnt signalling in crypts. YAP dampens Wnt signals by restricting DVL nuclear translocation during regenerative growth. Finally, we provide evidence that YAP is silenced in a subset of highly aggressive and undifferentiated human colorectal carcinomas, and that its expression can restrict the growth of colorectal carcinoma xenografts. Collectively, our work describes a novel mechanistic paradigm for how proliferative signals are counterbalanced in regenerating tissues. Additionally, our findings have important implications for the targeting of YAP in human malignancies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536889/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536889/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barry, Evan R -- Morikawa, Teppei -- Butler, Brian L -- Shrestha, Kriti -- de la Rosa, Rosemarie -- Yan, Kelley S -- Fuchs, Charles S -- Magness, Scott T -- Smits, Ron -- Ogino, Shuji -- Kuo, Calvin J -- Camargo, Fernando D -- 1K08DK096048/DK/NIDDK NIH HHS/ -- 1U01DK085527/DK/NIDDK NIH HHS/ -- AR064036/AR/NIAMS NIH HHS/ -- K08 DK096048/DK/NIDDK NIH HHS/ -- P01CA87969/CA/NCI NIH HHS/ -- P30 DK049216/DK/NIDDK NIH HHS/ -- P50CA127003/CA/NCI NIH HHS/ -- R01 AR064036/AR/NIAMS NIH HHS/ -- R01 CA131426/CA/NCI NIH HHS/ -- R01 CA151993/CA/NCI NIH HHS/ -- R01 DK091427/DK/NIDDK NIH HHS/ -- U01 DK085527/DK/NIDDK NIH HHS/ -- England -- Nature. 2013 Jan 3;493(7430):106-10. doi: 10.1038/nature11693. Epub 2012 Nov 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Program and Department of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23178811" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Adaptor Proteins, Signal Transducing/deficiency/genetics/*metabolism ; Animals ; *Cell Proliferation ; Colorectal Neoplasms/genetics/metabolism/pathology ; Genes, Tumor Suppressor ; Humans ; Intestines/*cytology/physiology ; Mice ; Mice, Knockout ; Neoplasm Transplantation ; Phosphoproteins/deficiency/genetics/*metabolism ; Regeneration/*physiology ; Stem Cell Niche ; Stem Cells/*cytology/*metabolism ; Thrombospondins/genetics/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; Wnt Proteins/metabolism ; Wnt Signaling Pathway
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-07-06
    Description: Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711467/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711467/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Straussman, Ravid -- Morikawa, Teppei -- Shee, Kevin -- Barzily-Rokni, Michal -- Qian, Zhi Rong -- Du, Jinyan -- Davis, Ashli -- Mongare, Margaret M -- Gould, Joshua -- Frederick, Dennie T -- Cooper, Zachary A -- Chapman, Paul B -- Solit, David B -- Ribas, Antoni -- Lo, Roger S -- Flaherty, Keith T -- Ogino, Shuji -- Wargo, Jennifer A -- Golub, Todd R -- P50CA093683/CA/NCI NIH HHS/ -- U54 CA112962/CA/NCI NIH HHS/ -- U54CA112962/CA/NCI NIH HHS/ -- UM1 CA186709/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jul 26;487(7408):500-4. doi: 10.1038/nature11183.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763439" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/pharmacology/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Cell Line, Tumor ; Coculture Techniques ; *Drug Resistance, Neoplasm/drug effects ; Hepatocyte Growth Factor/metabolism/*secretion ; Humans ; Indoles/pharmacology/therapeutic use ; Melanoma/drug therapy/genetics/*metabolism/pathology ; Molecular Targeted Therapy ; Mutation ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Proteomics ; Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics ; Proto-Oncogene Proteins c-met/antagonists & inhibitors/metabolism ; Signal Transduction/drug effects ; Stromal Cells/cytology/drug effects/metabolism/secretion ; Sulfonamides/pharmacology/therapeutic use ; Tumor Microenvironment/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
    Electronic Resource
    Electronic Resource
    Purification of human urinary erythropoietin
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 417 (1987), S. 178-182 
    Details
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0378-4347(87)80105-6
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  • 5
    Electronic Resource
    Electronic Resource
    On the orbital contribution to the neutron scattering
    Amsterdam : Elsevier
    Physics Letters A 57 (1976), S. 63-64 
    Details
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0375-9601(76)90455-2
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  • 6
    Electronic Resource
    Electronic Resource
    Simple and combination resonances of columns under periodic axial loads
    Amsterdam : Elsevier
    Journal of Sound and Vibration 33 (1974), S. 211-221 
    Details
    ISSN: 0022-460X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0022-460X(74)80107-0
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  • 7
    Electronic Resource
    Electronic Resource
    Ammonium Hydrogen Tartronate (1998)
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 54 (1998), S. 384-386 
    Details
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1107/S0108270197015126
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  • 8
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    Measurement of the variation of electron-to-proton mass ratio using ultracold molecules produced from laser-cooled atoms (2019)
    Springer Nature
    Details
    Publication Date: 2019
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 9
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    Force regulation of CD44-mediated rolling [Biophysics and Computational Biology] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-06-03
    Description: CD44 is the receptor for hyaluronan (HA) and mediates cell rolling under fluid shear stress. The HA-binding domain (HABD) of CD44 interconverts between a low-affinity, ordered (O) state and a high-affinity, partially disordered (PD) state, by the conformational change of the C-terminal region, which is connected to the plasma membrane....
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    FEL beam sharing systems for eight user's stations at the FELI (1996)
    Elsevier
    Details
    Publication Date: 1996-06-01
    Print ISSN: 0168-9002
    Electronic ISSN: 1872-9576
    Topics: Physics
    Published by Elsevier
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