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  • 1
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    Sequential cancer mutations in cultured human intestinal stem cells (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-04-30
    Description: Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain genetically and phenotypically stable. Here we utilize CRISPR/Cas9 technology for targeted gene modification of four of the most commonly mutated colorectal cancer genes (APC, P53 (also known as TP53), KRAS and SMAD4) in cultured human intestinal stem cells. Mutant organoids can be selected by removing individual growth factors from the culture medium. Quadruple mutants grow independently of all stem-cell-niche factors and tolerate the presence of the P53 stabilizer nutlin-3. Upon xenotransplantation into mice, quadruple mutants grow as tumours with features of invasive carcinoma. Finally, combined loss of APC and P53 is sufficient for the appearance of extensive aneuploidy, a hallmark of tumour progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drost, Jarno -- van Jaarsveld, Richard H -- Ponsioen, Bas -- Zimberlin, Cheryl -- van Boxtel, Ruben -- Buijs, Arjan -- Sachs, Norman -- Overmeer, Rene M -- Offerhaus, G Johan -- Begthel, Harry -- Korving, Jeroen -- van de Wetering, Marc -- Schwank, Gerald -- Logtenberg, Meike -- Cuppen, Edwin -- Snippert, Hugo J -- Medema, Jan Paul -- Kops, Geert J P L -- Clevers, Hans -- England -- Nature. 2015 May 7;521(7550):43-7. doi: 10.1038/nature14415. Epub 2015 Apr 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584CT Utrecht, The Netherlands [2] Cancer Genomics Netherlands, UMC Utrecht, 3584CG Utrecht, The Netherlands. ; 1] Cancer Genomics Netherlands, UMC Utrecht, 3584CG Utrecht, The Netherlands [2] Molecular Cancer Research, Centre for Molecular Medicine, UMC Utrecht, 3584CG, Utrecht, The Netherlands. ; 1] Cancer Genomics Netherlands, UMC Utrecht, 3584CG Utrecht, The Netherlands [2] Laboratory of Experimental Oncology and Radiobiology, Centre for Experimental Molecular Medicine, AMC, 1105AZ Amsterdam, The Netherlands. ; Department of Medical Genetics, UMC Utrecht, 3508AB Utrecht, The Netherlands. ; Department of Pathology, UMC Utrecht, 3584CX Utrecht, The Netherlands. ; 1] Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584CT Utrecht, The Netherlands [2] Cancer Genomics Netherlands, UMC Utrecht, 3584CG Utrecht, The Netherlands [3] Foundation Hubrecht Organoid Technology (HUB), 3584CT Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25924068" target="_blank"〉PubMed〈/a〉
    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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    Comment on "Dynamics of dpp signaling and proliferation control" (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-01-28
    Description: Wartlick et al. (Research Articles, 4 March 2011, p. 1154) reported that growth rates in the Drosophila wing disc correlate with increasing Dpp signaling levels, suggesting that the rate of Dpp increase determines the cell-cycle length. Contradicting their model, we found that cells in which the increase of Dpp signaling levels was genetically abrogated grew at rates comparable to those of wild-type cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwank, Gerald -- Yang, Schu-Fee -- Restrepo, Simon -- Basler, Konrad -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):401; author reply 401. doi: 10.1126/science.1210997.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282789" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Proliferation ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*growth & development/*metabolism ; Intercellular Signaling Peptides and Proteins/*metabolism ; *Signal Transduction ; Wings, Animal/*growth & development/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
    Electronic Resource
    Electronic Resource
    Copolymerization of dehydrated castor oil with styrene: Determination of reactivity ratios (1974)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 18 (1974), S. 2517-2526 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Dehydrated castor oil (DCO) has been used as a comonomer with styrene to determine reactivity ratios. The polymerization was a free-radical process in benzene, and the product was isolated by evaporation of the reaction mixture and by two precipitations into petroleum ether from benzene. The copolymer composition was determined by a saponification procedure. DCO was found to have a high chain transfer constant and a very low reactivity ratio (estimated at 0.086) compared to styrene (11.6). It was found that copolymerization is difficult to achieve in a system where the DCO concentration in the reaction mixture was above 20 mole-%.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1974.070180830
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