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Search: WFRF:(Evers Andreas) > (2010-2014)

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  • Gad, Helge, et al. (author)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Journal article (peer-reviewed)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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3.
  • Nyberg, Lars, 1962-, et al. (author)
  • Sustainability aspects of water regulation and flood risk reduction in Lake Vänern
  • 2014
  • In: Aquatic Ecosystem Health & Management. - : Taylor & Francis. - 1463-4988 .- 1539-4077. ; 17:4, s. 331-340
  • Journal article (peer-reviewed)abstract
    • A modern feature of flood risk management is to integrate ecological, economic and social aspects in risk prevention and mitigation. Risk-reducing measures can be in conflict with ecosystem functions and complicate upstream/downstream relations. Flood risks are also influenced by processes in the catchment, such as changes in climate and land-use, or increases of vulnerable urban areas. Lake Vänern in Sweden has high ecological and social values but is also flood-prone, which in this article has been analyzed from a perspective of sustainable development. Lake Vänern and the Göta älv River are used for drinking water supply, shipping, hydropower production, fishing, tourism, as a recipient for industries and wastewater plants, etc. The flood risks are connected to landslide and industrial risks. One interest at stake is the drinking water supply for 800,000 persons in the Gothenburg region. According to climate scenarios, flood risks will increase in the 21st century due to increased precipitation. Recent studies in the region were used to identify relevant interests and values connected to Lake Vänern. The study reveals differing interests in relation to water level regimes. From a flood protection perspective (risks around the lake and downstream to Gothenburg) a low and stable water level is beneficial. For shipping and hydropower, a stable medium-high water level is wanted, whereas from an ecosystem and landscape development perspective larger water level amplitudes are optimal. One out of a few reasons for this is the need to prevent a massive increase in vegetation in coastal areas. There are good reasons to have a broad decision-support, representing different values and interests, when the permanent water regulation scheme will be decided. This study also addresses the potential to reconcile the concept of flood risk management with that of a sustainable development.
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  • Result 1-3 of 3
Type of publication
journal article (2)
conference paper (1)
Type of content
peer-reviewed (3)
Author/Editor
Nyberg, Lars, 1962- (2)
Dahlström, Margareta ... (2)
Evers, Mariele (2)
Johansson, Lars (1)
Henriksson, Martin (1)
Johansson, Fredrik (1)
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Helleday, Thomas (1)
Loseva, Olga (1)
Artursson, Per (1)
Hammarström, Lars G. ... (1)
Svensson, Richard (1)
Jenmalm Jensen, Anni ... (1)
Lundbäck, Thomas (1)
Lundin, Cecilia (1)
Schultz, Niklas (1)
Gustafsson, Robert (1)
Axelsson, Hanna (1)
Altun, Mikael (1)
Jeppsson, Fredrik (1)
Djureinovic, Tatjana (1)
Stenmark, Pål (1)
Nilsson, Jonas A, 19 ... (1)
Wallner, Olov A. (1)
Gad, Helge (1)
Martens, Ulf (1)
Häggblad, Maria (1)
Lundgren, Bo (1)
Saleh, Aljona (1)
Einarsdottir, Bergli ... (1)
Gaugaz, Fabienne Z. (1)
Baranczewski, Pawel (1)
Berntsson, Ronnie P. ... (1)
Svensson, Linda M. (1)
Pham, Therese (1)
Scobie, Martin (1)
Höglund, Andreas (1)
Göktürk, Camilla (1)
Wiita, Elisee (1)
Vallin, Karl S. A. (1)
Jemth, Ann-Sofie (1)
Sanjiv, Kumar (1)
Desroses, Matthieu (1)
Kalderen, Christina (1)
Koolmeister, Tobias (1)
Homan, Evert J. (1)
Carreras-Puigvert, J ... (1)
Bräutigam, Lars (1)
Warpman Berglund, Ul ... (1)
Vikingsson, Svante (1)
Hagenkort, Anna (1)
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University
Karlstad University (2)
University of Gothenburg (1)
Uppsala University (1)
Stockholm University (1)
Linköping University (1)
Karolinska Institutet (1)
Language
English (3)
Research subject (UKÄ/SCB)
Natural sciences (3)
Medical and Health Sciences (1)

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