Now showing items 1-20 of 129

    • Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. 

      Natrajan, R; Wilkerson, PM; Marchiò, C; Piscuoglio, S; Ng, CK; Wai, P; Lambros, MB; Samartzis, EP; Dedes, KJ; Frankum, J; Bajrami, I; Kopec, A; Mackay, A; A'hern, R; Fenwick, K; Kozarewa, I; Hakas, J; Mitsopoulos, C; Hardisson, D; Lord, CJ; Kumar-Sinha, C; Ashworth, A; Weigelt, B; Sapino, A; Chinnaiyan, AM; Maher, CA; Reis-Filho, JS (2014-04)
      Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen ...
    • Titration of signalling output: insights into clinical combinations of MEK and AKT inhibitors. 

      Stewart, A; Thavasu, P; de Bono, JS; Banerji, U (2015-07)
      We aimed to understand the relative contributions of inhibiting MEK and AKT on cell growth to guide combinations of these agents.A panel of 20 cell lines was exposed to either the MEK inhibitor, PD0325901, or AKT inhibitor, ...
    • Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials. 

      Geuna, E; Roda, D; Rafii, S; Jimenez, B; Capelan, M; Rihawi, K; Montemurro, F; Yap, TA; Kaye, SB; De Bono, JS; Molife, LR; Banerji, U (2015-12)
      PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients.Retrospective ...
    • A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. 

      Dale, T; Clarke, PA; Esdar, C; Waalboer, D; Adeniji-Popoola, O; Ortiz-Ruiz, MJ; Mallinger, A; Samant, RS; Czodrowski, P; Musil, D; Schwarz, D; Schneider, K; Stubbs, M; Ewan, K; Fraser, E; TePoele, R; Court, W; Box, G; Valenti, M; de Haven Brandon, A; Gowan, S; Rohdich, F; Raynaud, F; Schneider, R; Poeschke, O; Blaukat, A; Workman, P; Schiemann, K; Eccles, SA; Wienke, D; Blagg, J (2015-12)
      There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT ...
    • AMPK-independent inhibition of human macrophage ER stress response by AICAR. 

      Boß, M; Newbatt, Y; Gupta, S; Collins, I; Brüne, B; Namgaladze, D (2016-01)
      Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty ...
    • Characterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions. 

      Puglisi, M; Stewart, A; Thavasu, P; Frow, M; Carreira, S; Minchom, A; Punwani, R; Bhosle, J; Popat, S; Ratoff, J; de Bono, J; Yap, TA; O''Brien, M; Banerji, U (2016-01)
      We hypothesised that it was possible to quantify phosphorylation of important nodes in the phosphatidylinositol 3-kinase (PI3K) pathway in cancer cells isolated from pleural effusions of patients with non-small cell lung ...
    • Copy Number Profiling of Brazilian Astrocytomas. 

      Bidinotto, LT; Torrieri, R; Mackay, A; Almeida, GC; Viana-Pereira, M; Cruvinel-Carloni, A; Spina, ML; Campanella, NC; Pereira de Menezes, W; Clara, CA; Becker, AP; Jones, C; Reis, RM (2016-01)
      Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of ...
    • Antibody-drug conjugates--an emerging class of cancer treatment. 

      Diamantis, N; Banerji, U (2016-02)
      Antibody-drug conjugates (ADCs) are an emerging novel class of anticancer treatment agents that combines the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs. New linker technology associated ...
    • Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines. 

      Campbell, J; Ryan, CJ; Brough, R; Bajrami, I; Pemberton, HN; Chong, IY; Costa-Cabral, S; Frankum, J; Gulati, A; Holme, H; Miller, R; Postel-Vinay, S; Rafiq, R; Wei, W; Williamson, CT; Quigley, DA; Tym, J; Al-Lazikani, B; Fenton, T; Natrajan, R; Strauss, SJ; Ashworth, A; Lord, CJ (2016-03-02)
      One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase ...
    • Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. 

      Mansfield, DC; Kyula, JN; Rosenfelder, N; Chao-Chu, J; Kramer-Marek, G; Khan, AA; Roulstone, V; McLaughlin, M; Melcher, AA; Vile, RG; Pandha, HS; Khoo, V; Harrington, KJ (2016-04)
      Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy ...
    • Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library. 

      Welford, AJ; Caldwell, JJ; Liu, M; Richards, M; Brown, N; Lomas, C; Tizzard, GJ; Pitak, MB; Coles, SJ; Eccles, SA; Raynaud, FI; Collins, I (2016-04)
      The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical ...
    • Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach. 

      Innocenti, P; Woodward, HL; Solanki, S; Naud, S; Westwood, IM; Cronin, N; Hayes, A; Roberts, J; Henley, AT; Baker, R; Faisal, A; Mak, GW; Box, G; Valenti, M; De Haven Brandon, A; O'Fee, L; Saville, H; Schmitt, J; Matijssen, B; Burke, R; van Montfort, RL; Raynaud, FI; Eccles, SA; Linardopoulos, S; Blagg, J; Hoelder, S (2016-04-07)
      Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ...
    • Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70. 

      Cheeseman, MD; Westwood, IM; Barbeau, O; Rowlands, M; Dobson, S; Jones, AM; Jeganathan, F; Burke, R; Kadi, N; Workman, P; Collins, I; van Montfort, RL; Jones, K (2016-05)
      HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought ...
    • Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma. 

      George, SL; Falzone, N; Chittenden, S; Kirk, SJ; Lancaster, D; Vaidya, SJ; Mandeville, H; Saran, F; Pearson, AD; Du, Y; Meller, ST; Denis-Bacelar, AM; Flux, GD (2016-05)
      Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate ...
    • Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer. 

      Weller, A; O'Brien, ME; Ahmed, M; Popat, S; Bhosle, J; McDonald, F; Yap, TA; Du, Y; Vlahos, I; deSouza, NM (2016-05)
      Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing ...
    • Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. 

      Ferraldeschi, R; Welti, J; Powers, MV; Yuan, W; Smyth, T; Seed, G; Riisnaes, R; Hedayat, S; Wang, H; Crespo, M; Nava Rodrigues, D; Figueiredo, I; Miranda, S; Carreira, S; Lyons, JF; Sharp, S; Plymate, SR; Attard, G; Wallis, N; Workman, P; de Bono, JS (2016-05)
      Resistance to available hormone therapies in prostate cancer has been associated with alternative splicing of androgen receptor (AR) and specifically, the expression of truncated and constitutively active AR variant 7 ...
    • Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses. 

      Lorente, D; Omlin, A; Zafeiriou, Z; Nava-Rodrigues, D; Pérez-López, R; Pezaro, C; Mehra, N; Sheridan, E; Figueiredo, I; Riisnaes, R; Miranda, S; Crespo, M; Flohr, P; Mateo, J; Altavilla, A; Ferraldeschi, R; Bianchini, D; Attard, G; Tunariu, N; de Bono, J (2016-05-05)
      The urgent need for castration-resistant prostate cancer molecular characterization to guide treatment has been constrained by the disease's predilection to metastasize primarily to bone. We hypothesized that the use of ...
    • 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19. 

      Mallinger, A; Schiemann, K; Rink, C; Sejberg, J; Honey, MA; Czodrowski, P; Stubbs, M; Poeschke, O; Busch, M; Schneider, R; Schwarz, D; Musil, D; Burke, R; Urbahns, K; Workman, P; Wienke, D; Clarke, PA; Raynaud, FI; Eccles, SA; Esdar, C; Rohdich, F; Blagg, J (2016-06)
      We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid ...
    • Development of molecularly targeted agents and immunotherapies in small cell lung cancer. 

      Sharp, A; Bhosle, J; Abdelraouf, F; Popat, S; O'Brien, M; Yap, TA (2016-06)
      Small cell lung cancer (SCLC) is a smoking-induced malignancy with multiple toxin-associated mutations, which accounts for 15% of all lung cancers. It remains a clinical challenge with a rapid doubling time, early dissemination ...
    • Immuno-oncology combinations: raising the tail of the survival curve. 

      Harris, SJ; Brown, J; Lopez, J; Yap, TA (2016-06)
      There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small ...