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  • 1
    Publication Date: 2012-08-17
    Description: Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712624/" 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/PMC3712624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Florian L -- Colla, Simona -- Aquilanti, Elisa -- Manzo, Veronica E -- Genovese, Giannicola -- Lee, Jaclyn -- Eisenson, Daniel -- Narurkar, Rujuta -- Deng, Pingna -- Nezi, Luigi -- Lee, Michelle A -- Hu, Baoli -- Hu, Jian -- Sahin, Ergun -- Ong, Derrick -- Fletcher-Sananikone, Eliot -- Ho, Dennis -- Kwong, Lawrence -- Brennan, Cameron -- Wang, Y Alan -- Chin, Lynda -- DePinho, Ronald A -- 3 P01 CA095616-08S1/CA/NCI NIH HHS/ -- 57006984/Howard Hughes Medical Institute/ -- P01 CA095616/CA/NCI NIH HHS/ -- P01CA95616/CA/NCI NIH HHS/ -- T32-CA009361/CA/NCI NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):337-42. doi: 10.1038/nature11331.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895339" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers, Tumor/deficiency/genetics ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Chromosomes, Human, Pair 1/genetics ; DNA-Binding Proteins/deficiency/genetics ; Enzyme Inhibitors ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genes, Essential/*genetics ; Genes, Tumor Suppressor ; Glioblastoma/*drug therapy/*genetics/pathology ; Homozygote ; Humans ; Hydroxamic Acids/pharmacology/therapeutic use ; Mice ; Molecular Targeted Therapy/*methods ; Neoplasm Transplantation ; Phosphonoacetic Acid/analogs & derivatives/pharmacology/therapeutic use ; Phosphopyruvate Hydratase/antagonists & inhibitors/deficiency/genetics/metabolism ; RNA, Small Interfering/genetics ; Sequence Deletion/*genetics ; Tumor Suppressor Proteins/deficiency/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: 2015-07-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Florian -- Colla, Simona -- Aquilanti, Elisa -- Manzo, Veronica E -- Genovese, Giannicola -- Lee, Jaclyn -- Eisenson, Daniel -- Narurkar, Rujuta -- Deng, Pingna -- Nezi, Luigi -- Lee, Michelle -- Hu, Baoli -- Hu, Jian -- Sahin, Ergun -- Ong, Derrick -- Fletcher-Sananikone, Eliot -- Ho, Dennis -- Kwong, Lawrence -- Brennan, Cameron -- Wang, Y Alan -- Chin, Lynda -- DePinho, Ronald A -- England -- Nature. 2015 Sep 10;525(7568):278. doi: 10.1038/nature14609. Epub 2015 Jul 8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26153864" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 87 (2000), S. 7885-7891 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A full-band Monte Carlo model is used to investigate the probability distribution functions of impact ionization path length and impact ionization energy for electrons and holes in GaAs. The simulations show that the soft ionization threshold energy in GaAs allows impact ionization to occur at energies much higher than the band gap. As a result, secondary carriers have a shorter dead space than newly injected carriers. The ionization path length distributions narrow at higher fields, producing a more deterministic impact ionization process in thin devices. The model is also used to simulate avalanche multiplication and noise in submicron homojunction GaAs p+-i-n+ diodes. The predicted mean multiplication, 〈M〉 and excess noise factor, F are in quantitative agreement with the experimental results, in which F decreases as the length of multiplication region is reduced. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 335 (1988), S. 733-735 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] When retinoic acid (RA) is applied to the anterior side of the chick limb bud, mirror-symmetrical pattern duplications are produced9'10. The resulting double posterior limbs have up to six digits instead of the normal three. The behaviour of this compound mimics precisely the effects of grafting ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 72 (1998), S. 232-234 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We use a Monte Carlo model to investigate the improvement of avalanche noise performance in thin p+-i-n+ GaAs diodes. The model predicts a decrease in avalanche noise as the multiplication length decreases from 1.0 to 0.05 μm, in good agreement with recent experimental measurements. Our simulations suggest that electron initiated multiplication in short devices has inherently reduced noise despite higher feedback from hole ionization, as compared to long devices. This low noise behavior results from the narrower ionization probability distribution and larger dead space effect as a higher operating electric field needed in short devices. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 83 (1998), S. 3426-3428 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Avalanche multiplication and noise in 1.0, 0.5, 0.1, and 0.05 μm GaAs p+-i-n+ diodes have been calculated for both electron and hole initiated multiplication using a simple model which incorporates a randomly-generated ionization path length (RPL) and a hard-threshold dead space. We find that the mean multiplication obtained using this RPL model is in excellent agreement, even for the shortest structure, with that obtained from an analytical-band structure Monte Carlo (MC) model, which incorporates soft-threshold effects. However, it predicts slightly lower avalanche noise in the shorter devices. This difference results from the narrower ionization path length probability distribution and larger dead space of the hard-threshold RPL model at high electric fields as compared to the more realistic distribution function associated with the relatively sophisticated MC model. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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