ArticlePloS one2014
A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- The structure of a NEMO construct engineered for screening reveals novel determinants of inhibition.Structure (London, England : 1993) · 2025Article
- Improving human cancer therapy through the evaluation of pet dogs.Nature reviews. Cancer · 2020Review
- NF-κB inhibitor, NEMO-binding domain peptide attenuates intervertebral disc degeneration.The spine journal : official journal of the North American Spine Society · 2020Article
- Targeting NF-κB Signaling for Multiple Myeloma.Cancers · 2020Review
- Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.International journal of molecular sciences · 2020Article
- The Genetic and Molecular Basis for Canine Models of Human Leukemia and Lymphoma.Frontiers in oncology · 2020Review
- Targeting IKKα kinase to prevent tumor progression and therapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies.The AAPS journal · 2019Review
- Targeting NEDD8-activating enzyme is a new approach to treat canine diffuse large B-cell lymphoma.Veterinary and comparative oncology · 2018Article
- Anti-Inflammatory Peptide Attenuates Edema and Promotes BMP-2-Induced Bone Formation in Spine Fusion.Tissue engineering. Part A · 2018Article
- Cell-Permeable Bicyclic Peptidyl Inhibitors against NEMO-IκB Kinase Interaction Directly from a Combinatorial Library.Journal of the American Chemical Society · 2018Article
- Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors.Cells · 2018Review
- Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation.PLoS biology · 2018Article
- NEMO peptide inhibits the growth of pancreatic ductal adenocarcinoma by blocking NF-κB activation.Cancer letters · 2017Article
- A model of the onset of the senescence associated secretory phenotype after DNA damage induced senescence.PLoS computational biology · 2017Article
- Tumor suppression via inhibition of SWI/SNF complex-dependent NF-κB activation.Scientific reports · 2017Article
- Enhancing the Cell Permeability and Metabolic Stability of Peptidyl Drugs by Reversible Bicyclization.Angewandte Chemie (International ed. in English) · 2017Article
- The NF-κB Pathway and Cancer Stem Cells.Cells · 2016Review
- Dogs as a Model for Cancer.Annual review of animal biosciences · 2016Review
- Targeting NF-κB in glioblastoma: A therapeutic approach.Science advances · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma (DLBCL) is a common, aggressive and poorly chemoresponsive subtype of DLBCL, characterized by constitutive canonical NF-κB signaling. Inhibition of NF-κB signaling leads to apoptosis of ABC-DLBCL cell lines, suggesting targeted disruption of this pathway may have therapeutic relevance. The selective IKK inhibitor, NEMO Binding Domain (NBD) peptide effectively blocks constitutive NF-κB activity and induces apoptosis in ABC-DLBCL cells in vitro. Here we used a comparative approach to determine the safety and efficacy of systemic NBD peptide to inhibit constitutive NF-κB signaling in privately owned dogs with spontaneous newly diagnosed or relapsed ABC-like DLBCL. Malignant lymph nodes biopsies were taken before and twenty-four hours after peptide administration to determine biological effects. Intravenous administration of <2 mg/kg NBD peptide was safe and inhibited constitutive canonical NF-κB activity in 6/10 dogs. Reductions in mitotic index and Cyclin D expression also occurred in a subset of dogs 24 hours post peptide and in 3 dogs marked, therapeutically beneficial histopathological changes were identified. Mild, grade 1 toxicities were noted in 3 dogs at the time of peptide administration and one dog developed transient subclinical hepatopathy. Long term toxicities were not identified. Pharmacokinetic data suggested rapid uptake of peptide into tissues. No significant hematological or biochemical toxicities were identified. Overall the results from this phase I study indicate that systemic administration of NBD peptide is safe and effectively blocks constitutive NF-κB signaling and reduces malignant B cell proliferation in a subset of dogs with ABC-like DLBCL. These results have potential translational relevance for human ABC-DLBCL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.