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  • 1
    Publication Date: 2008-08-22
    Description: Myc is a pleiotropic basic helix-loop-helix leucine zipper transcription factor that coordinates expression of the diverse intracellular and extracellular programs that together are necessary for growth and expansion of somatic cells. In principle, this makes inhibition of Myc an attractive pharmacological approach for treating diverse types of cancer. However, enthusiasm has been muted by lack of direct evidence that Myc inhibition would be therapeutically efficacious, concerns that it would induce serious side effects by inhibiting proliferation of normal tissues, and practical difficulties in designing Myc inhibitory drugs. We have modelled genetically both the therapeutic impact and the side effects of systemic Myc inhibition in a preclinical mouse model of Ras-induced lung adenocarcinoma by reversible, systemic expression of a dominant-interfering Myc mutant. We show that Myc inhibition triggers rapid regression of incipient and established lung tumours, defining an unexpected role for endogenous Myc function in the maintenance of Ras-dependent tumours in vivo. Systemic Myc inhibition also exerts profound effects on normal regenerating tissues. However, these effects are well tolerated over extended periods and rapidly and completely reversible. Our data demonstrate the feasibility of targeting Myc, a common downstream conduit for many oncogenic signals, as an effective, efficient and tumour-specific cancer therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485609/" 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/PMC4485609/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soucek, Laura -- Whitfield, Jonathan -- Martins, Carla P -- Finch, Andrew J -- Murphy, Daniel J -- Sodir, Nicole M -- Karnezis, Anthony N -- Swigart, Lamorna Brown -- Nasi, Sergio -- Evan, Gerard I -- 2R01 CA98018/CA/NCI NIH HHS/ -- R01 CA098018/CA/NCI NIH HHS/ -- R01 CA098018-05/CA/NCI NIH HHS/ -- R01 CA098018-06/CA/NCI NIH HHS/ -- R01 CA098018-07/CA/NCI NIH HHS/ -- T32 CA108462/CA/NCI NIH HHS/ -- T32 CA108462-01/CA/NCI NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):679-83. doi: 10.1038/nature07260. Epub 2008 Aug 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143-0875, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18716624" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/genetics/metabolism/pathology/therapy ; Animals ; Gastrointestinal Tract/cytology/metabolism/pathology ; Genes, Dominant/genetics ; Genes, ras ; *Genetic Therapy ; Lung Neoplasms/genetics/metabolism/pathology/*therapy ; Male ; Mice ; *Models, Biological ; Mutation/genetics ; Oncogene Protein p21(ras)/metabolism ; Proto-Oncogene Proteins c-myc/*antagonists & inhibitors/*genetics/metabolism ; Skin/cytology/metabolism/pathology ; Testis/cytology/metabolism/pathology ; Transgenes/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2017-02-16
    Description: Microstructure and mechanical properties of Ta-B-C nanocrystalline layers prepared by magnetron sputtering were studied. DC magnetron sputtering was used to prepare thin layers on rotated substrates. Various deposition parameters were tested. Microstructure of layers was studied by means of scanning and transmission electron microscopy on thin lamellar cross sections prepared using a focussed ion beam. Both undisturbed layers and the volume under relatively large indentation prints (load of 1 N) were observed. The microstructure observations were correlated with mechanical properties characterized by means of nanoindentation experiments in both the static and the dynamic loading regime. Elastic modulus, indentation hardness and fracture resistance of prepared nanostructured coatings were evaluated and discussed.
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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