• Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution. 

  Fisher, R; Horswell, S; Rowan, A; Salm, MP; de Bruin, EC; Gulati, S; McGranahan, N; Stares, M; Gerlinger, M; Varela, I; Crockford, A; Favero, F; Quidville, V; André, F; Navas, C; Grönroos, E; Nicol, D; Hazell, S; Hrouda, D; O'Brien, T; Matthews, N; Phillimore, B; Begum, S; Rabinowitz, A; Biggs, J; Bates, PA; McDonald, NQ; Stamp, G; Spencer-Dene, B; Hsieh, JJ; Xu, J; Pickering, L; Gore, M; Larkin, J; Swanton, C (2014-08-27)

  BACKGROUND:Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. RESULTS:We perform whole exome sequencing on four clear ...
• 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. ...
• A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer. 

  Glasspool, RM; Brown, R; Gore, ME; Rustin, GJS; McNeish, IA; Wilson, RH; Pledge, S; Paul, J; Mackean, M; Hall, GD; Gabra, H; Halford, SER; Walker, J; Appleton, K; Ullah, R; Kaye, S; Scottish Gynaecological Trials Group (2014-04)

  BACKGROUND:Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis ...
• Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials. 

  Rafii, S; Roda, D; Geuna, E; Jimenez, B; Rihawi, K; Capelan, M; Yap, TA; Molife, LR; Kaye, SB; de Bono, JS; Banerji, U (2015-04)

  Novel antitumor therapies against the PI3K-AKT-mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. Although these agents are not known ...
• Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis. 

  Natrajan, R; Sailem, H; Mardakheh, FK; Arias Garcia, M; Tape, CJ; Dowsett, M; Bakal, C; Yuan, Y (2016-02-16)

  The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess ...
• Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models. 

  O'Connor, JPB; Boult, JKR; Jamin, Y; Babur, M; Finegan, KG; Williams, KJ; Little, RA; Jackson, A; Parker, GJM; Reynolds, AR; Waterton, JC; Robinson, SP (2016-02)

  There is a clinical need for noninvasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning, and therapy monitoring. Oxygen-enhanced MRI (OE-MRI) is an emerging imaging technique for ...
• RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance. 

  Lionarons, DA; Hancock, DC; Rana, S; East, P; Moore, C; Murillo, MM; Carvalho, J; Spencer-Dene, B; Herbert, E; Stamp, G; Damry, D; Calado, DP; Rosewell, I; Fritsch, R; Neubig, RR; Molina-Arcas, M; Downward, J (2019-07)

  RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S activates PAK, AKT, and a ...
• Metal-based imaging agents: progress towards interrogating neurodegenerative disease. 

  Sedgwick, AC; Brewster, JT; Harvey, P; Iovan, DA; Smith, G; He, X-P; Tian, H; Sessler, JL; James, TD (2020-05)

  Central nervous system (CNS) neurodegeneration is defined by a complex series of pathological processes that ultimately lead to death. The precise etiology of these disorders remains unknown. Recent efforts show that a ...
• Fibroblastic Reticular Cells Control Conduit Matrix Deposition during Lymph Node Expansion. 

  Martinez, VG; Pankova, V; Krasny, L; Singh, T; Makris, S; White, IJ; Benjamin, AC; Dertschnig, S; Horsnell, HL; Kriston-Vizi, J; Burden, JJ; Huang, PH; Tape, CJ; Acton, SE (2019-11)

  Lymph nodes (LNs) act as filters, constantly sampling peripheral cues. This is facilitated by the conduit network, a tubular structure of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells ...
• A decade of clinical development of PARP inhibitors in perspective. 

  Mateo, J; Lord, CJ; Serra, V; Tutt, A; Balmaña, J; Castroviejo-Bermejo, M; Cruz, C; Oaknin, A; Kaye, SB; de Bono, JS (2019-09)

  Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce ...
• Multidisciplinary interventions in a specialist Drug Development Unit to improve family history documentation and onward referral of patients with advanced cancer to cancer genetics services. 

  Moss, CA; Cojocaru, E; Hanwell, J; Ward, S; Xu, W; van Zyl, M; O'Leary, L; de Bono, JS; Banerji, U; Kaye, SB; Minchom, A; George, AJ; Lopez, J; McVeigh, TP (2019-06)

  BACKGROUND:Molecular aberrations in cancer may represent therapeutic targets, and, if arising from the germline, may impact further cancer risk management in patients and their blood relatives. Annually, 600-700 patients ...
• Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer. 

  Oza, A; Kaye, S; Van Tornout, J; Sessa, C; Gore, M; Naumann, RW; Hirte, H; Colombo, N; Chen, J; Gorla, S; Poondru, S; Singh, M; Steinberg, J; Yuen, G; Banerjee, S (2018-05)

  BACKGROUND:Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1 receptor and insulin receptor, in combination with weekly paclitaxel, may improve clinical outcomes compared with paclitaxel alone in patients ...
• Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer. 

  Murillo, MM; Rana, S; Spencer-Dene, B; Nye, E; Stamp, G; Downward, J (2018-12)

  RAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110α impairs RAS-mutant-onc ...
• Synthesis of a benzoxazinthione derivative of tanaproget and pharmacological evaluation for PET imaging of PR expression. 

  Allott, L; Miranda, C; Hayes, A; Raynaud, F; Cawthorne, C; Smith, G (2019-01-10)

  BACKGROUND:The histological evaluation of estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer lesions from biopsy tissue can stratify patients to receive endocrine therapy. Furthermore, PR ...
• Publisher Correction: Cancer genetics, precision prevention and a call to action. 

  Turnbull, C; Sud, A; Houlston, RS (2019-01)

  In the version of this article originally published, there was an error in the second-to-last sentence of the abstract. In this sentence, the final phrase "to identify carriers of first-wave gene mutation carriers" should ...
• Structural basis for translocation by AddAB helicase-nuclease and its arrest at χ sites. 

  Krajewski, WW; Fu, X; Wilkinson, M; Cronin, NB; Dillingham, MS; Wigley, DB (2014-04)

  In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence χ (Chi) and is catalysed by either an AddAB- or RecBCD-type ...
• A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. 

  Mateo, J; Olmos, D; Dumez, H; Poondru, S; Samberg, NL; Barr, S; Van Tornout, JM; Jie, F; Sandhu, S; Tan, DS; Moreno, V; LoRusso, PM; Kaye, SB; Schöffski, P (2016-04)

  The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK activation, which may be abrogated by mTORC2 inhibition. ...
• Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models. 

  Burley, TA; Da Pieve, C; Martins, CD; Ciobota, DM; Allott, L; Oyen, WJG; Harrington, KJ; Smith, G; Kramer-Marek, G (2019-03)

  In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR monoclonal ...
• Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse 

  Brada, M; Hoang-Xuan, K; Rampling, R; Dietrich, PY; Dirix, LY; Macdonald, D; Heimans, JJ; Zonnenberg, BA; Bravo-Marques, JM; Henriksson, R; Stupp, R; Yue, N; Bruner, J; Dugan, M; Rao, S; Zaknoen, S (KLUWER ACADEMIC PUBL, 2001-02)

  Background: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens ...
• Nested allosteric interactions in the cytoplasmic chaperonin containing TCP-1 

  Kafri, G; Willison, KR; Horovitz, A (2001-02)

  Initial rates of ATP hydrolysis by the chaperonin containing TCP-1 (CCT) from bovine testis were measured as a function of ATP concentration. Two allosteric transitions are observed: one at relatively low concentrations ...

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