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265 results on '"Corbett, Simon"'

1. A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

Author

Kanagaratnam, Prapa, Francis, Darrel P., Chamie, Daniel, Coyle, Clare, Marynina, Alena, Katritsis, George, Paiva, Patricia, Szigeti, Matyas, Cole, Graham, de Andrade Nunes, David, Howard, James, Esper, Rodrigo, Khan, Masood, More, Ranjit, Barreto, Guilherme, Meneguz-Moreno, Rafael, Arnold, Ahran, Nowbar, Alexandra, Kaura, Amit, Mariveles, Myril, March, Katherine, Shah, Jaymin, Nijjer, Sukhjinder, Lip, Gregory Y.H., Mills, Nicholas, Camm, A. John, Cooke, Graham S., Corbett, Simon J., Llewelyn, Martin J., Ghanima, Waleed, Toshner, Mark, Peters, Nicholas, Petraco, Ricardo, Al-Lamee, Rasha, Boshoff, Ana Sousa Marcelino, Durkina, Margarita, Malik, Iqbal, Ruparelia, Neil, Cornelius, Victoria, and Shun-Shin, Matthew

Published
2023
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2. Understanding the mechanisms of action of pyrrolobenzodiazepine dimer-based antibody-drug conjugates

Author

Corbett, Simon Edward

Subjects
616.99
Abstract

DNA interstrand cross-linking (ICL) Pyrrolobenzodiazepine (PBD) dimers are being investigated clinically as warheads for antibody-drug conjugates (ADCs). Understanding their molecular mechanisms of action will help inform the clinical application and future development of this class of targeted anti-cancer agents. PBD dimer-containing ADCs, targeting CD19 or CD22, were investigated in vitro by comparing cell-surface receptor expression, binding and internalisation kinetics, ICL formation and how these correlated with growth inhibition and apoptosis. The effect of mouse strain immunodeficiency on antibody biodistribution and ADC efficacy was investigated using in vivo imaging, and the contribution of the tumour microenvironment on protease-cleavable ADC efficacy was explored by depletion of tumour-associated macrophages (TAMs), or replacing the cleavable linker. Cells with acquired resistance to PBD dimer or PBD dimer-delivering ADCs were generated using sub-lethal, pulsed treatments. The mechanisms of resistance were investigated by measuring DNA ICLs, transporter gene expression, and antibody internalisation. Combinations of ADC and conventional drugs were studied for cytotoxic synergy and effects on antigen expression and DNA ICL formation. The anti-CD19 ADC was more cytotoxic than the anti-CD22 ADC, and growth inhibition correlated with DNA ICL formation, but not cell surface target antigen expression. ADCs were sequestered in non-target organs in severely immunodeficient mouse strains, reducing in vivo efficacy. Target-independent interaction of protease-cleavable ADCs with TAMs in the tumour microenvironment contributed to the anti-tumour response. Specific ABC transporters were upregulated in all cell lines with acquired resistance to either ADC or PBD, while antigen expression and internalisation were unaffected. Inhibitors or siRNA knockdown of ABCC2 and ABCG2 were able to restore sensitivity. Combinations of ADC with chemotherapeutic drugs that increase target antigen expression or hypomethylate DNA were synergistic in vitro. These data include a number of potentially clinically relevant findings that could influence treatment strategy, as well as future ADC design and pre-clinical development.

Published
2020

4. Figure S8 from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Author

Zammarchi, Francesca, primary, Havenith, Karin E., primary, Sachini, Nikoleta, primary, Janghra, Narinder, primary, Chivers, Simon, primary, Idusogie, Esohe, primary, Gaudio, Eugenio, primary, Tarantelli, Chiara, primary, Bertelli, Francois, primary, Santos, Kathleen, primary, Tyrer, Peter, primary, Corbett, Simon, primary, Spriano, Filippo, primary, Golino, Gaetanina, primary, Cascione, Luciano, primary, Bertoni, Francesco, primary, Hartley, John A., primary, and van Berkel, Patrick H., primary

Published
2024
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5. Supplementary Data from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Author

Zammarchi, Francesca, primary, Havenith, Karin E., primary, Sachini, Nikoleta, primary, Janghra, Narinder, primary, Chivers, Simon, primary, Idusogie, Esohe, primary, Gaudio, Eugenio, primary, Tarantelli, Chiara, primary, Bertelli, Francois, primary, Santos, Kathleen, primary, Tyrer, Peter, primary, Corbett, Simon, primary, Spriano, Filippo, primary, Golino, Gaetanina, primary, Cascione, Luciano, primary, Bertoni, Francesco, primary, Hartley, John A., primary, and van Berkel, Patrick H., primary

Published
2024
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6. Data from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Author

Zammarchi, Francesca, primary, Havenith, Karin E., primary, Sachini, Nikoleta, primary, Janghra, Narinder, primary, Chivers, Simon, primary, Idusogie, Esohe, primary, Gaudio, Eugenio, primary, Tarantelli, Chiara, primary, Bertelli, Francois, primary, Santos, Kathleen, primary, Tyrer, Peter, primary, Corbett, Simon, primary, Spriano, Filippo, primary, Golino, Gaetanina, primary, Cascione, Luciano, primary, Bertoni, Francesco, primary, Hartley, John A., primary, and van Berkel, Patrick H., primary

Published
2024
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7. ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Author

Zammarchi, Francesca, primary, Havenith, Karin E., additional, Sachini, Nikoleta, additional, Janghra, Narinder, additional, Chivers, Simon, additional, Idusogie, Esohe, additional, Gaudio, Eugenio, additional, Tarantelli, Chiara, additional, Bertelli, Francois, additional, Santos, Kathleen, additional, Tyrer, Peter, additional, Corbett, Simon, additional, Spriano, Filippo, additional, Golino, Gaetanina, additional, Cascione, Luciano, additional, Bertoni, Francesco, additional, Hartley, John A., additional, and van Berkel, Patrick H., additional

Published
2024
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12. Association between troponin level and medium-term mortality in 20 000 hospital patients

Author

Hinton, Jonathan, primary, Mariathas, Mark Nihal, additional, Gabara, Lavinia, additional, Allan, Rick, additional, Nicholas, Zoe, additional, Kwok, Chun Shing, additional, Ramamoorthy, Sanjay, additional, Calver, Alison, additional, Corbett, Simon, additional, Jabbour, Richard J, additional, Mahmoudi, Michael, additional, Rawlins, John, additional, Sirohi, Rohit, additional, Wilkinson, James Richard, additional, Cook, Paul, additional, Martin, Glen Philip, additional, Mamas, Mamas A, additional, and Curzen, Nick, additional

Published
2023
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13. Association between troponin level and medium term mortality in 20,000 hospital patients

Author

Hinton, Jonathan, Mariathas, Mark, Gabara, Lavinia, Allan, Rick, Nicholas, Zoe, Kwok, Chun Shing, Ramamoorthy, Sanjay, Calver, Alison, Corbett, Simon, Jabbour, Richard J., Mahmoudi, Michael, Rawlins, John, Sirohi, Rohit, Wilkinson, J., Cook, Paul, Martin, Glen P., Mamas, Mamas, and Curzen, Nicholas

Abstract

Introduction: cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test.Method: this prospective observational study included 20,000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. Results: A total of 20,000 patients were included in the analysis and 18,282 of these (91.4%) did not have a clinical indication for cTnI testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% versus 12.3% pConclusion: in a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium term cardiovascular and non-cardiovascular mortality in the statistical model tested.

Published
2023

19. Data from Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody–Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer

Author

Cho, Song, primary, Zammarchi, Francesca, primary, Williams, David G., primary, Havenith, Carin E.G., primary, Monks, Noel R., primary, Tyrer, Peter, primary, D'Hooge, Francois, primary, Fleming, Ryan, primary, Vashisht, Kapil, primary, Dimasi, Nazzareno, primary, Bertelli, Francois, primary, Corbett, Simon, primary, Adams, Lauren, primary, Reinert, Halla W., primary, Dissanayake, Sandamali, primary, Britten, Charles E., primary, King, Wanda, primary, Dacosta, Karma, primary, Tammali, Ravinder, primary, Schifferli, Kevin, primary, Strout, Patrick, primary, Korade, Martin, primary, Masson Hinrichs, Mary Jane, primary, Chivers, Simon, primary, Corey, Eva, primary, Liu, He, primary, Kim, Sae, primary, Bander, Neil H., primary, Howard, Philip W., primary, Hartley, John A., primary, Coats, Steve, primary, Tice, David A., primary, Herbst, Ronald, primary, and van Berkel, Patrick H., primary

Published
2023
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20. Supplementary Methods from Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody–Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer

Author

Cho, Song, primary, Zammarchi, Francesca, primary, Williams, David G., primary, Havenith, Carin E.G., primary, Monks, Noel R., primary, Tyrer, Peter, primary, D'Hooge, Francois, primary, Fleming, Ryan, primary, Vashisht, Kapil, primary, Dimasi, Nazzareno, primary, Bertelli, Francois, primary, Corbett, Simon, primary, Adams, Lauren, primary, Reinert, Halla W., primary, Dissanayake, Sandamali, primary, Britten, Charles E., primary, King, Wanda, primary, Dacosta, Karma, primary, Tammali, Ravinder, primary, Schifferli, Kevin, primary, Strout, Patrick, primary, Korade, Martin, primary, Masson Hinrichs, Mary Jane, primary, Chivers, Simon, primary, Corey, Eva, primary, Liu, He, primary, Kim, Sae, primary, Bander, Neil H., primary, Howard, Philip W., primary, Hartley, John A., primary, Coats, Steve, primary, Tice, David A., primary, Herbst, Ronald, primary, and van Berkel, Patrick H., primary

Published
2023
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21. Supplementary Tables S1 to S4 from Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody–Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer

Author

Cho, Song, primary, Zammarchi, Francesca, primary, Williams, David G., primary, Havenith, Carin E.G., primary, Monks, Noel R., primary, Tyrer, Peter, primary, D'Hooge, Francois, primary, Fleming, Ryan, primary, Vashisht, Kapil, primary, Dimasi, Nazzareno, primary, Bertelli, Francois, primary, Corbett, Simon, primary, Adams, Lauren, primary, Reinert, Halla W., primary, Dissanayake, Sandamali, primary, Britten, Charles E., primary, King, Wanda, primary, Dacosta, Karma, primary, Tammali, Ravinder, primary, Schifferli, Kevin, primary, Strout, Patrick, primary, Korade, Martin, primary, Masson Hinrichs, Mary Jane, primary, Chivers, Simon, primary, Corey, Eva, primary, Liu, He, primary, Kim, Sae, primary, Bander, Neil H., primary, Howard, Philip W., primary, Hartley, John A., primary, Coats, Steve, primary, Tice, David A., primary, Herbst, Ronald, primary, and van Berkel, Patrick H., primary

Published
2023
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25. Supplementary Figures S1-S7 from Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody–Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer

Author

Cho, Song, primary, Zammarchi, Francesca, primary, Williams, David G., primary, Havenith, Carin E.G., primary, Monks, Noel R., primary, Tyrer, Peter, primary, D'Hooge, Francois, primary, Fleming, Ryan, primary, Vashisht, Kapil, primary, Dimasi, Nazzareno, primary, Bertelli, Francois, primary, Corbett, Simon, primary, Adams, Lauren, primary, Reinert, Halla W., primary, Dissanayake, Sandamali, primary, Britten, Charles E., primary, King, Wanda, primary, Dacosta, Karma, primary, Tammali, Ravinder, primary, Schifferli, Kevin, primary, Strout, Patrick, primary, Korade, Martin, primary, Masson Hinrichs, Mary Jane, primary, Chivers, Simon, primary, Corey, Eva, primary, Liu, He, primary, Kim, Sae, primary, Bander, Neil H., primary, Howard, Philip W., primary, Hartley, John A., primary, Coats, Steve, primary, Tice, David A., primary, Herbst, Ronald, primary, and van Berkel, Patrick H., primary

Published
2023
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27. Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine

Author

Hartley, John A., Flynn, Michael J., Bingham, John P., Corbett, Simon, Reinert, Halla, Tiberghien, Arnaud, Masterson, Luke A., Antonow, Dyeison, Adams, Lauren, Chowdhury, Sajidah, Williams, David G., Mao, Shenlan, Harper, Jay, Havenith, Carin E. G., Zammarchi, Francesca, Chivers, Simon, van Berkel, Patrick H., and Howard, Philip W.

Published
2018
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29. 169 High-sensitivity troponin is a biomarker of medium term mortality in 20,000 consecutive hospital patients undergoing a blood test for any reason

Author

Hinton, Jonathan, primary, Mariathas, Mark, additional, Gabara, Lavinia, additional, Allan, Rick, additional, Nicholas, Zoe, additional, Kwok, Chun Shing, additional, Ramamoorthy, Sanjay, additional, Calver, Alison, additional, Corbett, Simon, additional, Rawlins, John, additional, Simpson, Iain, additional, Wilkinson, James, additional, Sirohi, Rohit, additional, Mahmoudi, Michael, additional, Martin, Glen, additional, Cook, Paul, additional, Mamas, Mamas, additional, and Curzen, Nick, additional

Published
2022
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35. Cardiac MRI of myocardial salvage at the peri-infarct border zones after primary coronary intervention

Author

O'Regan, Declan P., Ahmed, Rizwan, Neuwirth, Clare, Tan, Yvonne, Durighel, Giuliana, Hajnal, Joseph V., Nadra, Imad, Corbett, Simon J., and Cook, Stuart A.

Subjects
Heart attack -- Diagnosis, Magnetic resonance imaging -- Methods, Biological sciences
Abstract

The purpose of this study was to use cardiac MRI to define the morphology of the reversibly injured peri-infarct border zone in patients treated with primary percutaneous coronary intervention (PPCI) for acute ST elevation myocardial infarction. In 15 patients, T2-weighted myocardial edema imaging was used to identify the ischemic bed or area at risk (AAR), and late gadolinium enhancement imaging was used to measure infarct size. Images were coregistered, and the boundaries of edema and necrosis were defined using an edge-detection methodology. We observed that infarction always involved the subendocardium but showed variable transmural extension within the AAR. The mean infarct size was 22 [+ or -] 19% (range: 8-48%), and the mean AAR was 34 [+ or -] 12% (range: 20-57%). The infarcted myocardium was always smaller than the ischemic AAR and involved between 34% and 99% (mean 72 [+ or -] 21%) of the ischemic bed primarily due to variation in transmural infarct extension. Although a lateral border zone of potentially viable myocardium was often present, its extent was limited (range: 0-11 mm, mean: 5 [+ or -] 4 mm). As a result of this, infarcts occupied the majority (range: 70-100%, mean: 82 [+ or -] 13%) of the width of the AAR. The mean fractional wall thickening in the infarcted, peri-infarcted, and remote myocardium was 3.6 [+ or -] 16.0%, 40.5 [+ or -] 26.4%, and 88.2 [+ or -] 39.3%, respectively. These findings demonstrate that myocardial salvage is largely determined by epicardial limitation of the infarct within the ischemic AAR after PPCI. The lateral boundaries of necrosis approximate to the lateral extent of the ischemic bed and systolic wall motion abnormalities extend well beyond the infarct border zone. angioplasty; magnetic resonance imaging; myocardial infarction

Published
2009

37. 184 Association between high-sensitivity troponin and one year mortality in 20,000 consecutive hospital patients undergoing a blood test for any reason

Author

Hinton, Jonathan, primary, Mariathas, Mark, additional, Gabara, Lavinia, additional, Allan, Rick, additional, Nicholas, Zoe, additional, Kwok, Chun Shing, additional, Ramamoorthy, Sanjay, additional, Calver, Alison, additional, Corbett, Simon, additional, Rawlins, John, additional, Simpson, Iain, additional, Wilkinson, James, additional, Sirohi, Rohit, additional, Mahmoudi, Michael, additional, Martin, Glen, additional, Cook, Paul, additional, Mamas, Mamas, additional, and Curzen, Nick, additional

Published
2021
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