Owen A. O’Connor
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View article: Management of T‐cell malignancies: Bench‐to‐bedside targeting of epigenetic biology
Management of T‐cell malignancies: Bench‐to‐bedside targeting of epigenetic biology Open
The peripheral T‐cell lymphomas (PTCL) are the only disease for which four histone deacetylase (HDAC) inhibitors have been approved globally as single agents. Although it is not clear why the PTCL exhibit such a vulnerability to these drug…
View article: Perspectives on the Mature T-Cell Lymphomas in the Middle East: A Comprehensive Review of the Present Status
Perspectives on the Mature T-Cell Lymphomas in the Middle East: A Comprehensive Review of the Present Status Open
Background: T-cell lymphomas (TCLs) are rare and aggressive malignancies associated with poor outcomes, often because of the development of acquired drug resistance as well as intolerance to the established and often toxic chemotherapy reg…
View article: Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: results from the PETAL consortium
Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: results from the PETAL consortium Open
Variances in global access to drugs and treatment practices make it challenging to understand the benefit of contemporary therapies in patients with relapsed and refractory (R/R) mature T-cell and natural killer–cell lymphomas (MTCL and MN…
View article: Preclinical Development of a Romidepsin Nanoparticle Demonstrates Superior Tolerability and Efficacy in Models of Human T-Cell Lymphoma and Large Granular Lymphocyte Leukemia
Preclinical Development of a Romidepsin Nanoparticle Demonstrates Superior Tolerability and Efficacy in Models of Human T-Cell Lymphoma and Large Granular Lymphocyte Leukemia Open
Histone deacetylase (HDAC) inhibitors are a widely recognized and valued treatment option for patients with relapsed or refractory peripheral T cell lymphomas (PTCL). Romidepsin is a relatively selective Class I HDAC inhibitor originally a…
View article: Pooled analysis of pralatrexate single-agent studies in patients with relapsed/refractory peripheral T-cell lymphoma
Pooled analysis of pralatrexate single-agent studies in patients with relapsed/refractory peripheral T-cell lymphoma Open
Patients with relapsed or refractory (R/R) mature natural killer cell and T-cell lymphoma have limited treatment options. To evaluate pralatrexate’s performance and factors influencing its safety and efficacy in R/R peripheral T-cell lymph…
View article: Integration of Machine-Learning Approaches to Estimate Survival for Patients with Mature T-Cell and NK-Cell Lymphomas
Integration of Machine-Learning Approaches to Estimate Survival for Patients with Mature T-Cell and NK-Cell Lymphomas Open
View article: 706 An Audit of Antibiotic Prescribing in Acute Pancreatitis and Introduction of a Patient Safety and Cost Saving Diagnostic Tool
706 An Audit of Antibiotic Prescribing in Acute Pancreatitis and Introduction of a Patient Safety and Cost Saving Diagnostic Tool Open
Background In managing acute pancreatitis it is challenging to distinguish systemic inflammatory response syndrome (SIRS) from bacterial infection, contributing to inappropriate use of antibiotics, which are only recommended in cases of in…
View article: Pembrolizumab in combination with epigenetic therapy is safe and active in heavily treated patients with peripheral T‐cell lymphoma and cutaneous T‐cell lymphoma
Pembrolizumab in combination with epigenetic therapy is safe and active in heavily treated patients with peripheral T‐cell lymphoma and cutaneous T‐cell lymphoma Open
Introduction: Peripheral T-cell lymphomas are uniquely sensitive to epigenetic modifiers. We have shown that decitabine and 5-azacytidine (Marchi et al.; Br. J. Haematol. 171; 2015) induce the expression of cancer testis antigens in pre-cl…
View article: Identifying the mechanistic differences between hypomethylating agents for the treatment of peripheral T cell lymphoma
Identifying the mechanistic differences between hypomethylating agents for the treatment of peripheral T cell lymphoma Open
Introduction: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of malignancies that share a unifying feature of epigenetic dysregulation. Recent evidence suggests that PTCL, unlike other forms of cancer or even lymphom…
View article: Synthesis and Preclinical Development of a Promising Novel Romidepsin Nanoparticle for the Treatment of Peripheral T‐Cell Lymphoma (PTCL)
Synthesis and Preclinical Development of a Promising Novel Romidepsin Nanoparticle for the Treatment of Peripheral T‐Cell Lymphoma (PTCL) Open
Introduction: The HDAC inhibitors are important drugs for the treatment of PTCL. While these drugs produce ORR of 25–30% with short PFS, responses can last over a year. There is still debate on the optimal ways to use HDAC inhibitors. Most…
View article: Supplementary Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin
Supplementary Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin Open
Supplementary Figures 1-7 and Supplementary Table 1
View article: HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models
HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models Open
Both PD1/PD-L1 and CD47 blockades have demonstrated limited activity in most subtypes of NHL save NK/T-cell lymphoma. The hemotoxicity with anti-CD47 agents in the clinic has been speculated to account for their limitations. Herein we desc…
View article: Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin
Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin Open
Histone deacetylase inhibitors (HDACi) induce hyperacetylation of histones by blocking HDAC catalytic sites. Despite regulatory approvals in hematological malignancies, limited solid tumor clinical activity has constrained their potential,…
View article: Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin
Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin Open
Histone deacetylase inhibitors (HDACi) induce hyperacetylation of histones by blocking HDAC catalytic sites. Despite regulatory approvals in hematological malignancies, limited solid tumor clinical activity has constrained their potential,…
View article: Supplementary Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin
Supplementary Data from R-Loop–Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin Open
Supplementary Figures 1-7 and Supplementary Table 1
View article: Supplementary Figure Legend from Development and Characterization of a Novel CD19CherryLuciferase (CD19CL) Transgenic Mouse for the Preclinical Study of B-Cell Lymphomas
Supplementary Figure Legend from Development and Characterization of a Novel CD19CherryLuciferase (CD19CL) Transgenic Mouse for the Preclinical Study of B-Cell Lymphomas Open
PDF file, 43KB.
View article: Data from A Phase I Single-Agent Study of Twice-Weekly Consecutive-Day Dosing of the Proteasome Inhibitor Carfilzomib in Patients with Relapsed or Refractory Multiple Myeloma or Lymphoma
Data from A Phase I Single-Agent Study of Twice-Weekly Consecutive-Day Dosing of the Proteasome Inhibitor Carfilzomib in Patients with Relapsed or Refractory Multiple Myeloma or Lymphoma Open
Purpose: Carfilzomib is a next-generation, selective, proteasome inhibitor with clinical activity in relapsed and/or refractory multiple myeloma. The objectives of this phase I study were to establish the safety, tolerability, pharm…
View article: Supplementary Figure 1 from Development and Characterization of a Novel CD19CherryLuciferase (CD19CL) Transgenic Mouse for the Preclinical Study of B-Cell Lymphomas
Supplementary Figure 1 from Development and Characterization of a Novel CD19CherryLuciferase (CD19CL) Transgenic Mouse for the Preclinical Study of B-Cell Lymphomas Open
PDF file, 432KB, PCR genotyping analysis of CD19cherryluciferase transgenic founders. PCR products of the targeted and wild type alleles of the CD19 locus in two transgenic founders. The PCR conditions for the left arm insertion were: 95{d…
View article: Supplemental Figure 1 from Dual Targeting of Protein Degradation Pathways with the Selective HDAC6 Inhibitor ACY-1215 and Bortezomib Is Synergistic in Lymphoma
Supplemental Figure 1 from Dual Targeting of Protein Degradation Pathways with the Selective HDAC6 Inhibitor ACY-1215 and Bortezomib Is Synergistic in Lymphoma Open
Peripheral blood mononuclear cells (PBMCs) were separated from whole blood by Ficoll-Paque layering. (A) Concentration : effect relationship was determined for ACY-1215 at 24 and 48 hours in PBMCs. No cytotoxicity was observed after 24 and…
View article: Data from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Data from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma Open
Purpose:ADCT-402 (loncastuximab tesirine) is an antibody–drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab t…
View article: Data from Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies
Data from Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies Open
Purpose:TTI-621 (SIRPα-IgG1 Fc) is a novel checkpoint inhibitor that activates antitumor activity by blocking the CD47 “don't eat me” signal. This first-in-human phase I study (NCT02663518) evaluated the safety and activity of TTI-621 in r…
View article: Supplementary Data from Pralatrexate Is Synergistic with the Proteasome Inhibitor Bortezomib in <i>In vitro</i> and <i>In vivo</i> Models of T-Cell Lymphoid Malignancies
Supplementary Data from Pralatrexate Is Synergistic with the Proteasome Inhibitor Bortezomib in <i>In vitro</i> and <i>In vivo</i> Models of T-Cell Lymphoid Malignancies Open
Supplementary Data from Pralatrexate Is Synergistic with the Proteasome Inhibitor Bortezomib in In vitro and In vivo Models of T-Cell Lymphoid Malignancies
View article: Supplementary Tables 1-6, Supplementary Figure Legend from Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma
Supplementary Tables 1-6, Supplementary Figure Legend from Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma Open
Table A1. Prior therapies received (agents received by >5 patients); Table A2. Summary of pevonedistat plasma pharmacokinetic parameters on days 1 and 9 of cycle 1 on schedule A (administration on days 1, 2, 8, 9 of 21-day cycles); Table A…
View article: Supplementary Data from Romidepsin and Belinostat Synergize the Antineoplastic Effect of Bortezomib in Mantle Cell Lymphoma
Supplementary Data from Romidepsin and Belinostat Synergize the Antineoplastic Effect of Bortezomib in Mantle Cell Lymphoma Open
Supplementary Data from Romidepsin and Belinostat Synergize the Antineoplastic Effect of Bortezomib in Mantle Cell Lymphoma
View article: Supplemental Table 2 from The Novel IKK2 Inhibitor LY2409881 Potently Synergizes with Histone Deacetylase Inhibitors in Preclinical Models of Lymphoma through the Downregulation of NF-κB
Supplemental Table 2 from The Novel IKK2 Inhibitor LY2409881 Potently Synergizes with Histone Deacetylase Inhibitors in Preclinical Models of Lymphoma through the Downregulation of NF-κB Open
Supplemental Table 2. Representative synergy index of LY2409881 with lymphoma active drugs.
View article: Supplementary Materials from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Supplementary Materials from A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody–Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma Open
Supplementary Materials
View article: Data from Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma
Data from Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma Open
Purpose: Evaluate the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of the first-in-class investigational NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK-924/MLN4924) in patients with rel…
View article: Supplemental Figure 1 from Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib
Supplemental Figure 1 from Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib Open
Standard error values for ACY-1215 plus ibrutinib combinations in cell lines and primary human lymphoma samples. Viability was measured by CellTiter-Glo. Each experiment was performed in triplicate and repeated at least 2 times. The standa…
View article: Data from Preclinical Pharmacologic Evaluation of Pralatrexate and Romidepsin Confirms Potent Synergy of the Combination in a Murine Model of Human T-cell Lymphoma
Data from Preclinical Pharmacologic Evaluation of Pralatrexate and Romidepsin Confirms Potent Synergy of the Combination in a Murine Model of Human T-cell Lymphoma Open
Purpose: T-cell lymphomas (TCL) are aggressive diseases, which carry a poor prognosis. The emergence of new drugs for TCL has created a need to survey these agents in a rapid and reproducible fashion, to prioritize combinations whic…
View article: Supplemental Table 1 from The Novel IKK2 Inhibitor LY2409881 Potently Synergizes with Histone Deacetylase Inhibitors in Preclinical Models of Lymphoma through the Downregulation of NF-κB
Supplemental Table 1 from The Novel IKK2 Inhibitor LY2409881 Potently Synergizes with Histone Deacetylase Inhibitors in Preclinical Models of Lymphoma through the Downregulation of NF-κB Open
Supplemental Table 1. IC50 of LY2409881 in lymphoma cell lines.