Now showing items 1-11 of 11

    • The anticonvulsive Phenhydan<sup>®</sup> suppresses extrinsic cell death. 

      Moerke, C; Jaco, I; Dewitz, C; Müller, T; Jacobsen, AV; Gautheron, J; Fritsch, J; Schmitz, J; Bräsen, JH; Günther, C; Murphy, JM; Kunzendorf, U; Meier, P; Krautwald, S (2019-09)
      Different forms of regulated cell death-like apoptosis and necroptosis contribute to the pathophysiology of clinical conditions including ischemia-reperfusion injury, myocardial infarction, sepsis, and multiple sclerosis. ...
    • Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects. 

      Brody, LP; Sahuri-Arisoylu, M; Parkinson, JR; Parkes, HG; So, PW; Hajji, N; Thomas, EL; Frost, GS; Miller, AD; Bell, JD (2017-01)
      Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a ...
    • The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. 

      Walton, MI; Eve, PD; Hayes, A; Henley, AT; Valenti, MR; De Haven Brandon, AK; Box, G; Boxall, KJ; Tall, M; Swales, K; Matthews, TP; McHardy, T; Lainchbury, M; Osborne, J; Hunter, JE; Perkins, ND; Aherne, GW; Reader, JC; Raynaud, FI; Eccles, SA; Collins, I; Garrett, MD (2016-01)
      CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently ...
    • Dichloroacetate induces autophagy in colorectal cancer cells and tumours. 

      Lin, G; Hill, DK; Andrejeva, G; Boult, JKR; Troy, H; Fong, A-CLFWT; Orton, MR; Panek, R; Parkes, HG; Jafar, M; Koh, D-M; Robinson, SP; Judson, IR; Griffiths, JR; Leach, MO; Eykyn, TR; Chung, Y-L (2014-07)
      <h4>Background</h4>Dichloroacetate (DCA) has been found to have antitumour properties.<h4>Methods</h4>We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT ...
    • MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy. 

      Beloueche-Babari, M; Wantuch, S; Casals Galobart, T; Koniordou, M; Parkes, HG; Arunan, V; Chung, Y-L; Eykyn, TR; Smith, PD; Leach, MO (2017-11)
      Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination ...
    • MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death. 

      Jaco, I; Annibaldi, A; Lalaoui, N; Wilson, R; Tenev, T; Laurien, L; Kim, C; Jamal, K; Wicky John, S; Liccardi, G; Chau, D; Murphy, JM; Brumatti, G; Feltham, R; Pasparakis, M; Silke, J; Meier, P (2017-06)
      TNF is an inflammatory cytokine that upon binding to its receptor, TNFR1, can drive cytokine production, cell survival, or cell death. TNFR1 stimulation causes activation of NF-κB, p38α, and its downstream effector kinase ...
    • Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and CDK9 inhibitor. 

      Whittaker, SR; Barlow, C; Martin, MP; Mancusi, C; Wagner, S; Self, A; Barrie, E; Te Poele, R; Sharp, S; Brown, N; Wilson, S; Jackson, W; Fischer, PM; Clarke, PA; Walton, MI; McDonald, E; Blagg, J; Noble, M; Garrett, MD; Workman, P (2018-03)
      Deregulation of the cyclin-dependent kinases (CDKs) has been implicated in the pathogenesis of multiple cancer types. Consequently, CDKs have garnered intense interest as therapeutic targets for the treatment of cancer. ...
    • Promoter capture Hi-C-based identification of recurrent noncoding mutations in colorectal cancer. 

      Orlando, G; Law, PJ; Cornish, AJ; Dobbins, SE; Chubb, D; Broderick, P; Litchfield, K; Hariri, F; Pastinen, T; Osborne, CS; Taipale, J; Houlston, RS (2018-10)
      Efforts are being directed to systematically analyze the non-coding regions of the genome for cancer-driving mutations<sup>1-6</sup>. cis-regulatory elements (CREs) represent a highly enriched subset of the non-coding ...
    • RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation. 

      Liccardi, G; Ramos Garcia, L; Tenev, T; Annibaldi, A; Legrand, AJ; Robertson, D; Feltham, R; Anderton, H; Darding, M; Peltzer, N; Dannappel, M; Schünke, H; Fava, LL; Haschka, MD; Glatter, T; Nesvizhskii, A; Schmidt, A; Harris, PA; Bertin, J; Gough, PJ; Villunger, A; Silke, J; Pasparakis, M; Bianchi, K; Meier, P (2019-02)
      Receptor-interacting protein kinase (RIPK) 1 functions as a key mediator of tissue homeostasis via formation of Caspase-8 activating ripoptosome complexes, positively and negatively regulating apoptosis, necroptosis, and ...
    • Silencing of HSP90 cochaperone AHA1 expression decreases client protein activation and increases cellular sensitivity to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin. 

      Holmes, JL; Sharp, SY; Hobbs, S; Workman, P (2008-02)
      AHA1 (activator of HSP90 ATPase) is a cochaperone of the ATP-dependent molecular chaperone, HSP90, which is involved in the maturation, stabilization/degradation, and function of oncogenic proteins. HSP90 operates in a ...
    • Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. 

      Frentzas, S; Simoneau, E; Bridgeman, VL; Vermeulen, PB; Foo, S; Kostaras, E; Nathan, M; Wotherspoon, A; Gao, Z-H; Shi, Y; Van den Eynden, G; Daley, F; Peckitt, C; Tan, X; Salman, A; Lazaris, A; Gazinska, P; Berg, TJ; Eltahir, Z; Ritsma, L; Van Rheenen, J; Khashper, A; Brown, G; Nystrom, H; Sund, M; Van Laere, S; Loyer, E; Dirix, L; Cunningham, D; Metrakos, P; Reynolds, AR (2016-11)
      The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the ...