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14 results on '"Mangano, Raffaella"'

2. Erratum: Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer

Author

Drew, Yvette, primary, Ledermann, Jonathan, additional, Hall, Geoff, additional, Rea, Daniel, additional, Glasspool, Ros, additional, Highley, Martin, additional, Jayson, Gordon, additional, Sludden, Julieann, additional, Murray, James, additional, Jamieson, David, additional, Halford, Sarah, additional, Acton, Gary, additional, Backholer, Zoe, additional, Mangano, Raffaella, additional, Boddy, Alan, additional, Curtin, Nicola, additional, and Plummer, Ruth, additional

Published
2016
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3. Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer

Author

Drew, Yvette, primary, Ledermann, Jonathan, additional, Hall, Geoff, additional, Rea, Daniel, additional, Glasspool, Ros, additional, Highley, Martin, additional, Jayson, Gordon, additional, Sludden, Julieann, additional, Murray, James, additional, Jamieson, David, additional, Halford, Sarah, additional, Acton, Gary, additional, Backholer, Zoe, additional, Mangano, Raffaella, additional, Boddy, Alan, additional, Curtin, Nicola, additional, and Plummer, Ruth, additional

Published
2016
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4. Erratum: Corrigendum: A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation

Author

Bergamini, Giovanna, primary, Bell, Kathryn, additional, Shimamura, Satoko, additional, Werner, Thilo, additional, Cansfield, Andrew, additional, Müller, Katrin, additional, Perrin, Jessica, additional, Rau, Christina, additional, Ellard, Katie, additional, Hopf, Carsten, additional, Doce, Carola, additional, Leggate, Daniel, additional, Mangano, Raffaella, additional, Mathieson, Toby, additional, O'Mahony, Alison, additional, Plavec, Ivan, additional, Rharbaoui, Faiza, additional, Reinhard, Friedrich, additional, Savitski, Mikhail M, additional, Ramsden, Nigel, additional, Hirsch, Emilio, additional, Drewes, Gerard, additional, Rausch, Oliver, additional, Bantscheff, Marcus, additional, and Neubauer, Gitte, additional

Published
2012
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5. A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation

Author

Bergamini, Giovanna, primary, Bell, Kathryn, additional, Shimamura, Satoko, additional, Werner, Thilo, additional, Cansfield, Andrew, additional, Müller, Katrin, additional, Perrin, Jessica, additional, Rau, Christina, additional, Ellard, Katie, additional, Hopf, Carsten, additional, Doce, Carola, additional, Leggate, Daniel, additional, Mangano, Raffaella, additional, Mathieson, Toby, additional, O'Mahony, Alison, additional, Plavec, Ivan, additional, Rharbaoui, Faiza, additional, Reinhard, Friedrich, additional, Savitski, Mikhail M, additional, Ramsden, Nigel, additional, Hirsch, Emilio, additional, Drewes, Gerard, additional, Rausch, Oliver, additional, Bantscheff, Marcus, additional, and Neubauer, Gitte, additional

Published
2012
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6. Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists

Author

Cramp, Sue, primary, Dyke, Hazel J., additional, Higgs, Christopher, additional, Clark, David E., additional, Gill, Matthew, additional, Savy, Pascal, additional, Jennings, Neil, additional, Price, Steve, additional, Lockey, Peter M., additional, Norman, Dennis, additional, Porres, Soraya, additional, Wilson, Francis, additional, Jones, Alison, additional, Ramsden, Nigel, additional, Mangano, Raffaella, additional, Leggate, Dan, additional, Andersson, Marie, additional, and Hale, Richard, additional

Published
2010
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7. O2-03-05 Proteomic analysis of amyloid precursor protein processing complexes in human neuroblastoma cells by tandem affinity purification

Author

Hopf, Carsten, primary, Angrand, Pierre-Olivier, additional, Gagneur, Julien, additional, Heffernan, Brian, additional, Mangano, Raffaella, additional, Pickard, Lisa, additional, Ruffner, Heinz, additional, O'Sullivan, Eithne, additional, Stein, Martin, additional, Thomas, Susie, additional, Volkel, Pamela, additional, Kuster, Bernhard, additional, Choudhary, Jyoti, additional, Rowley, Adele, additional, and Drewes, Gerard, additional

Published
2004
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8. A physical and functional map of the human TNF-α/NF-κB signal transduction pathway

Author

Bouwmeester, Tewis, primary, Bauch, Angela, additional, Ruffner, Heinz, additional, Angrand, Pierre-Olivier, additional, Bergamini, Giovanna, additional, Croughton, Karen, additional, Cruciat, Cristina, additional, Eberhard, Dirk, additional, Gagneur, Julien, additional, Ghidelli, Sonja, additional, Hopf, Carsten, additional, Huhse, Bettina, additional, Mangano, Raffaella, additional, Michon, Anne-Marie, additional, Schirle, Markus, additional, Schlegl, Judith, additional, Schwab, Markus, additional, Stein, Martin A., additional, Bauer, Andreas, additional, Casari, Georg, additional, Drewes, Gerard, additional, Gavin, Anne-Claude, additional, Jackson, David B., additional, Joberty, Gerard, additional, Neubauer, Gitte, additional, Rick, Jens, additional, Kuster, Bernhard, additional, and Superti-Furga, Giulio, additional

Published
2004
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11. A selective inhibitor reveals PI3K? dependence of TH17 cell differentiation.

Author

Bergamini, Giovanna, Bell, Kathryn, Shimamura, Satoko, Werner, Thilo, Cansfield, Andrew, Müller, Katrin, Perrin, Jessica, Rau, Christina, Ellard, Katie, Hopf, Carsten, Doce, Carola, Leggate, Daniel, Mangano, Raffaella, Mathieson, Toby, O'Mahony, Alison, Plavec, Ivan, Rharbaoui, Faiza, Reinhard, Friedrich, Savitski, Mikhail M, and Ramsden, Nigel

Subjects
CELL differentiation, LIPID metabolism, PHOSPHOINOSITIDES, AUTOIMMUNE diseases, CHEMICAL biology
Abstract

We devised a high-throughput chemoproteomics method that enabled multiplexed screening of 16,000 compounds against native protein and lipid kinases in cell extracts. Optimization of one chemical series resulted in CZC24832, which is to our knowledge the first selective inhibitor of phosphoinositide 3-kinase ? (PI3K?) with efficacy in in vitro and in vivo models of inflammation. Extensive target- and cell-based profiling of CZC24832 revealed regulation of interleukin-17-producing T helper cell (TH17) differentiation by PI3K?, thus reinforcing selective inhibition of PI3K? as a potential treatment for inflammatory and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Published
2012
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12. A physical and functional map of the human TNF-a/NF-?B signal transduction pathway.

Author

Bauch, Angela, Ruffner, Heinz, Angrand, Pierre-Olivier, Croughton, Karen, Cruciat, Cristina, Eberhard, Dirk, Gagneur, Julien, Ghidelli, Sonja, Mangano, Raffaella, Bouwmeester, Tewis, Bergamini, Giovanna, Hopf, Carsten, Huhse, Bettina, Michon, Anne-Marie, Schirle, Markus, Schlegl, Judith, Schwab, Markus, Stein, Martin A., Bauer, Andreas, and Casari, Georg

Subjects
CELLULAR signal transduction, TUMOR necrosis factors, NF-kappa B, LIQUID chromatography, MASS spectrometry
Abstract

Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-a triggers a signalling cascade, converging on the activation of the transcription factor NF-?B, which forms the basis for numerous physiological and pathological processes. Here we report the mapping of a protein interaction network around 32 known and candidate TNF-a/NF-?B pathway components by using an integrated approach comprising tandem affinity purification, liquid-chromatography tandem mass spectrometry, network analysis and directed functional perturbation studies using RNA interference. We identified 221 molecular associations and 80 previously unknown interactors, including 10 new functional modulators of the pathway. This systems approach provides significant insight into the logic of the TNF-a/NF-?B pathway and is generally applicable to other pathways relevant to human disease. [ABSTRACT FROM AUTHOR]

Published
2004
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13. Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer

Author

Gordon C Jayson, Gary Acton, Jonathan A. Ledermann, Geoff Hall, Sarah Halford, Martin Highley, Nicola J. Curtin, Ruth Plummer, Julieann Sludden, R.M. Glasspool, David Jamieson, Alan V. Boddy, Zoe Backholer, Daniel Rea, Raffaella Mangano, Yvette Drew, James W. Murray, Drew, Yvette, Ledermann, Jonathan, Hall, Geoff, Rea, Daniel, Glasspool, Ros, Highley, Martin, Jayson, Gordon, Sludden, Julieann, Murray, James, Jamieson, David, Halford, Sarah, Acton, Gary, Backholer, Zoe, Mangano, Raffaella, Boddy, Alan, Curtin, Nicola, and Plummer, Ruth

Subjects
0301 basic medicine, Cancer Research, Indoles, Poly (ADP-Ribose) Polymerase Inhibitor, Cohort Studies, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Tissue Distribution, mutation carriers, Ovarian Neoplasms, Manchester Cancer Research Centre, BRCA1 Protein, Middle Aged, Prognosis, poly(ADP-ribose) polymerase, polymerase, ovarian cancer, Oncology, 030220 oncology & carcinogenesis, Female, Corrigendum, Adult, Heterozygote, Poly ADP ribose polymerase, Breast Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Drug Administration Schedule, Olaparib, Young Adult, 03 medical and health sciences, Germline mutation, Breast cancer, breast cancer, medicine, Humans, Rucaparib, Germ-Line Mutation, Aged, Neoplasm Staging, BRCA2 Protein, Dose-Response Relationship, Drug, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, PARP inhibition, BRCA mutation, medicine.disease, rucaparib, 030104 developmental biology, chemistry, Immunology, Cancer research, business, Follow-Up Studies
Abstract

Background: Rucaparib is an orally available potent selective small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP) 1 and 2. Rucaparib induces synthetic lethality in cancer cells defective in the homologous recombination repair pathway including BRCA-1/2. We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers. Methods: Phase II, open-label, multicentre trial of rucaparib in proven BRCA-1/2 mutation carriers with advanced breast and or ovarian cancer, WHO PS 0–1 and normal organ function. Intravenous (i.v.) and subsequently oral rucaparib were assessed, using a range of dosing schedules, to determine the safety, tolerability, dose-limiting toxic effects and pharmacodynamic (PD) and pharmacokinetic (PK) profiles. Results: Rucaparib was well tolerated in patients up to doses of 480 mg per day and is a potent inhibitor of PARP, with sustained inhibition ⩾24 h after single doses. The i.v. rucaparib (intermittent dosing schedule) resulted in an objective response rate (ORR) of only 2% but with 41% (18 out of 44) patients achieved stable disease for ⩾12 weeks and 3 patients maintaining disease stabilisation for >52 weeks. The ORR for oral rucaparib (across all six dose levels) was 15%. In the oral cohorts, 81% (22 out of 27) of the patients had ovarian cancer and 12 out of 13, who were dosed continuously, achieved RECIST complete response/partial response (CR/PR) or stable disease (SD) ⩾12 weeks, with a median duration of response of 179 days (range 84–567 days). Conclusions: Rucaparib is well tolerated and results in high levels of PARP inhibition in surrogate tissues even at the lowest dose levels. Rucaparib is active in gBRCA-mutant ovarian cancer and this activity correlates with platinum-free interval. The key lessons learned from this study is that continuous rucaparib dosing is required for optimal response, the recommended phase 2 dose (RP2D) for continuous oral scheduling has not been established and requires further exploration and, thirdly, the use of a PD biomarker to evaluate dose–response has its limitations.

Published
2016

14. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.

Author

Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, and Superti-Furga G

Subjects
Animals, Carrier Proteins genetics, Carrier Proteins metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Line, Chaperonins, Chromatography, Affinity methods, Enzyme Activation, HSP90 Heat-Shock Proteins genetics, HSP90 Heat-Shock Proteins metabolism, Humans, I-kappa B Proteins isolation & purification, I-kappa B Proteins metabolism, MAP Kinase Kinase Kinase 3, MAP Kinase Kinase Kinases genetics, MAP Kinase Kinase Kinases metabolism, Macromolecular Substances, Mass Spectrometry methods, Models, Biological, Molecular Chaperones genetics, Molecular Chaperones metabolism, NF-kappa B genetics, NF-kappa B isolation & purification, Proteome analysis, RNA Interference, Receptors, Tumor Necrosis Factor metabolism, Tacrolimus Binding Proteins genetics, Tacrolimus Binding Proteins metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha isolation & purification, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Drosophila Proteins, NF-kappa B metabolism, Signal Transduction physiology, Tumor Necrosis Factor-alpha metabolism
Abstract

Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha triggers a signalling cascade, converging on the activation of the transcription factor NF-kappa B, which forms the basis for numerous physiological and pathological processes. Here we report the mapping of a protein interaction network around 32 known and candidate TNF-alpha/NF-kappa B pathway components by using an integrated approach comprising tandem affinity purification, liquid-chromatography tandem mass spectrometry, network analysis and directed functional perturbation studies using RNA interference. We identified 221 molecular associations and 80 previously unknown interactors, including 10 new functional modulators of the pathway. This systems approach provides significant insight into the logic of the TNF-alpha/NF-kappa B pathway and is generally applicable to other pathways relevant to human disease.

Published
2004
Full Text
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