Now showing items 1-20 of 22

    • Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. 

      Hill, RM; Kuijper, S; Lindsey, JC; Petrie, K; Schwalbe, EC; Barker, K; Boult, JKR; Williamson, D; Ahmad, Z; Hallsworth, A; Ryan, SL; Poon, E; Robinson, SP; Ruddle, R; Raynaud, FI; Howell, L; Kwok, C; Joshi, A; Nicholson, SL; Crosier, S; Ellison, DW; Wharton, SB; Robson, K; Michalski, A; Hargrave, D; Jacques, TS; Pizer, B; Bailey, S; Swartling, FJ; Weiss, WA; Chesler, L; Clifford, SC (2015-01)
      We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, ...
    • Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. 

      Dolman, MEM; Poon, E; Ebus, ME; den Hartog, IJM; van Noesel, CJM; Jamin, Y; Hallsworth, A; Robinson, SP; Petrie, K; Sparidans, RW; Kok, RJ; Versteeg, R; Caron, HN; Chesler, L; Molenaar, JJ (2015-11)
      Purpose MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted ...
    • Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance. 

      Jamin, Y; Eykyn, TR; Poon, E; Springer, CJ; Robinson, SP (2014-04)
      Purpose The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) ...
    • 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)
      Background Dichloroacetate (DCA) has been found to have antitumour properties.Methods We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 ...
    • Hypoxia and its therapeutic possibilities in paediatric cancers. 

      Bernauer, C; Man, YKS; Chisholm, JC; Lepicard, EY; Robinson, SP; Shipley, JM (2020-10-27)
      In tumours, hypoxia-a condition in which the demand for oxygen is higher than its availability-is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The ...
    • <i>In Vivo</i> Modeling of Chemoresistant Neuroblastoma Provides New Insights into Chemorefractory Disease and Metastasis. 

      Yogev, O; Almeida, GS; Barker, KT; George, SL; Kwok, C; Campbell, J; Zarowiecki, M; Kleftogiannis, D; Smith, LM; Hallsworth, A; Berry, P; Möcklinghoff, T; Webber, HT; Danielson, LS; Buttery, B; Calton, EA; da Costa, BM; Poon, E; Jamin, Y; Lise, S; Veal, GJ; Sebire, N; Robinson, SP; Anderson, J; Chesler, L (2019-10)
      Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant <i>in vivo</i> models has limited our insight into the ...
    • Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma. 

      Tucker, ER; Tall, JR; Danielson, LS; Gowan, S; Jamin, Y; Robinson, SP; Banerji, U; Chesler, L (2017-08)
      Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies; however, the presence of resistant mutations necessitates both the development of more ...
    • Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors. 

      Vaughan, L; Clarke, PA; Barker, K; Chanthery, Y; Gustafson, CW; Tucker, E; Renshaw, J; Raynaud, F; Li, X; Burke, R; Jamin, Y; Robinson, SP; Pearson, A; Maira, M; Weiss, WA; Workman, P; Chesler, L (2016-09)
      MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ...
    • Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma. 

      Jamin, Y; Glass, L; Hallsworth, A; George, R; Koh, D-M; Pearson, ADJ; Chesler, L; Robinson, SP (2014-01)
      The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. ...
    • Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography. 

      Li, J; Zormpas-Petridis, K; Boult, JKR; Reeves, EL; Heindl, A; Vinci, M; Lopes, F; Cummings, C; Springer, CJ; Chesler, L; Jones, C; Bamber, JC; Yuan, Y; Sinkus, R; Jamin, Y; Robinson, SP (2019-11)
      Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic ...
    • Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma. 

      Al-Saffar, NMS; Troy, H; Wong Te Fong, A-C; Paravati, R; Jackson, LE; Gowan, S; Boult, JKR; Robinson, SP; Eccles, SA; Yap, TA; Leach, MO; Chung, Y-L (2018-10-31)
      Background AKT is commonly overexpressed in tumours and plays an important role in the metabolic reprogramming of cancer. We have used magnetic resonance spectroscopy (MRS) to assess whether inhibition of AKT signalling ...
    • MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment. 

      Zormpas-Petridis, K; Jerome, NP; Blackledge, MD; Carceller, F; Poon, E; Clarke, M; McErlean, CM; Barone, G; Koers, A; Vaidya, SJ; Marshall, LV; Pearson, ADJ; Moreno, L; Anderson, J; Sebire, N; McHugh, K; Koh, D-M; Yuan, Y; Chesler, L; Robinson, SP; Jamin, Y (2019-06)
      Childhood neuroblastoma is a hypervascular tumor of neural origin, for which antiangiogenic drugs are currently being evaluated; however, predictive biomarkers of treatment response, crucial for successful delivery of ...
    • MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma. 

      King, D; Li, XD; Almeida, GS; Kwok, C; Gravells, P; Harrison, D; Burke, S; Hallsworth, A; Jamin, Y; George, S; Robinson, SP; Lord, CJ; Poon, E; Yeomanson, D; Chesler, L; Bryant, HE (2020-06-09)
      This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, ...
    • Noninvasive detection of carboxypeptidase G2 activity in vivo. 

      Jamin, Y; Smyth, L; Robinson, SP; Poon, ESC; Eykyn, TR; Springer, CJ; Leach, MO; Payne, GS (2011-05)
      The pseudomonad protein, carboxypeptidase G2 (CPG2), is a prodrug-activating enzyme utilized in the targeted chemotherapy strategies of antibody- and gene-directed enzyme prodrug therapy (ADEPT and GDEPT). We have developed ...
    • Noninvasive MRI Native T<sub>1</sub> Mapping Detects Response to <i>MYCN</i>-targeted Therapies in the Th-<i>MYCN</i> Model of Neuroblastoma. 

      Zormpas-Petridis, K; Poon, E; Clarke, M; Jerome, NP; Boult, JKR; Blackledge, MD; Carceller, F; Koers, A; Barone, G; Pearson, ADJ; Moreno, L; Anderson, J; Sebire, N; McHugh, K; Koh, D-M; Chesler, L; Yuan, Y; Robinson, SP; Jamin, Y (2020-08)
      Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies ...
    • Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma. 

      Poon, E; Liang, T; Jamin, Y; Walz, S; Kwok, C; Hakkert, A; Barker, K; Urban, Z; Thway, K; Zeid, R; Hallsworth, A; Box, G; Ebus, ME; Licciardello, MP; Sbirkov, Y; Lazaro, G; Calton, E; Costa, BM; Valenti, M; De Haven Brandon, A; Webber, H; Tardif, N; Almeida, GS; Christova, R; Boysen, G; Richards, MW; Barone, G; Ford, A; Bayliss, R; Clarke, PA; De Bono, J; Gray, NS; Blagg, J; Robinson, SP; Eccles, SA; Zheleva, D; Bradner, JE; Molenaar, J; Vivanco, I; Eilers, M; Workman, P; Lin, CY; Chesler, L (2020-11)
      The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ...
    • p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance. 

      Yogev, O; Barker, K; Sikka, A; Almeida, GS; Hallsworth, A; Smith, LM; Jamin, Y; Ruddle, R; Koers, A; Webber, HT; Raynaud, FI; Popov, S; Jones, C; Petrie, K; Robinson, SP; Keun, HC; Chesler, L (2016-05)
      Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ...
    • Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. 

      Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; Khan, K; Lampis, A; Eason, K; Huntingford, I; Burke, R; Rata, M; Koh, D-M; Tunariu, N; Collins, D; Hulkki-Wilson, S; Ragulan, C; Spiteri, I; Moorcraft, SY; Chau, I; Rao, S; Watkins, D; Fotiadis, N; Bali, M; Darvish-Damavandi, M; Lote, H; Eltahir, Z; Smyth, EC; Begum, R; Clarke, PA; Hahne, JC; Dowsett, M; de Bono, J; Workman, P; Sadanandam, A; Fassan, M; Sansom, OJ; Eccles, S; Starling, N; Braconi, C; Sottoriva, A; Robinson, SP; Cunningham, D; Valeri, N (2018-02)
      Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ...
    • Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform. 

      Almeida, GS; Panek, R; Hallsworth, A; Webber, H; Papaevangelou, E; Boult, JK; Jamin, Y; Chesler, L; Robinson, SP (2017-09)
      Background The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies. Here the utility and sensitivity of anatomical and functional MRI data/biomarkers acquired from ...
    • Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma. 

      Boult, JKR; Apps, JR; Hölsken, A; Hutchinson, JC; Carreno, G; Danielson, LS; Smith, LM; Bäuerle, T; Buslei, R; Buchfelder, M; Virasami, AK; Koers, A; Arthurs, OJ; Jacques, TS; Chesler, L; Martinez-Barbera, JP; Robinson, SP (2018-07)
      To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed ...